Lawrence Kingsley

The relation between viremia and clinical outcome in individuals infected with human immunodeficiency virus-type 1 (HIV-1) has important implications for therapeutic research and clinical care. HIV-1 RNA in plasma was quantified with a branched-DNA signal amplification assay as a measure of viral load in a cohort of 180 seropositive men studied for more than 10 years. The risk of acquired immunodeficiency syndrome (AIDS) and death in study subjects, including those with normal numbers of CD4+ T cells, was directly related to plasma viral load at study entry. Plasma viral load was a better predictor of progression to AIDS and death than was the number of CD4+ T cells.

2507 homosexual men who were seronegative for human immunodeficiency virus (HIV) at enrolment were followed for six months to elucidate risk factors for seroconversion to HIV. 95 (3·8%) seroconverted. Of men who did not engage in receptive anal intercourse within six months before baseline and in the six-month follow-up period, only 0·5% (3/646) seroconverted to HIV. By contrast, of men who engaged in receptive anal intercourse with two or more partners during each of these successive six-month intervals, 10·6% (58/548) seroconverted. No HIV seroconversions occurred in 220 homosexual men who did not practise receptive or insertive anal intercourse within twelve months before the follow-up visit. On multivariate analysis receptive anal intercourse was the only significant risk factor for seroconversion to HIV, the risk ratio increasing from 3-fold for one partner to 18-fold for five or more partners. Furthermore, data for the two successive six-month periods show that men who reduced or stopped the practice of receptive anal intercourse significantly lowered their risk of seroconversion to 3·2% and 1·8%, respectively. Receptive anal intercourse accounted for nearly all new HIV infections among the homosexual men enrolled in this study, and the hazards of this practice need to be emphasised in community educational projects.

Background: Coronary artery disease (CAD) has been associated with HIV infection, but data are not consistent. Objective: To determine whether HIV-infected men have more coronary atherosclerosis than uninfected men. Design: Cross-sectional study. Setting: Multicenter AIDS Cohort Study. Participants: HIV-infected (n = 618) and uninfected (n = 383) men who have sex with men who were aged 40 to 70 years, weighed less than 136 kg (200 lb), and had no history of coronary revascularization. Measurements: Presence and extent of coronary artery calcium (CAC) on noncontrast cardiac computed tomography (CT) and of any plaque; noncalcified, mixed, or calcified plaque; or stenosis on coronary CT angiography. Results: 1001 men had noncontrast CT, of whom 759 had coronary CT angiography. After adjustment for age, race, CT scanning center, and cohort, HIV-infected men had a greater prevalence of CAC (prevalence ratio [PR], 1.21 [95% CI, 1.08 to 1.35]; P = 0.001) and any plaque (PR, 1.14 [CI, 1.05 to 1.24]; P = 0.001), including noncalcified (PR, 1.28 [CI, 1.13 to 1.45]; P < 0.001) and mixed (PR, 1.35 [CI, 1.10 to 1.65]; P = 0.004) plaque, than uninfected men. Associations between HIV infection and any plaque or noncalcified plaque remained significant (P < 0.005) after CAD risk factor adjustment. HIV-infected men had a greater extent of noncalcified plaque after CAD risk factor adjustment (P = 0.026). They also had a greater prevalence of coronary artery stenosis greater than 50% (PR, 1.48 [CI, 1.06 to 2.07]; P = 0.020), but not after CAD risk factor adjustment. Longer duration of highly active antiretroviral therapy (PR, 1.09 [CI, 1.02 to 1.17]; P = 0.007) and lower nadir CD4+ T-cell count (PR, 0.80 [CI, 0.69 to 0.94]; P = 0.005) were associated with coronary stenosis greater than 50%. Limitation: Cross-sectional observational study design and inclusion of only men. Conclusion: Coronary artery plaque, especially noncalcified plaque, is more prevalent and extensive in HIV-infected men, independent of CAD risk factors. Primary Funding Source: National Heart, Lung, and Blood Institute and National Institute of Allergy and Infectious Diseases.

Objectives: Kaposi's sarcoma-associated herpesvirus (KSHV), a newly discovered human gammaherpesvirus, is found in the majority of KS lesions from patients with and without AIDS. Peripheral blood mononuclear cells (PBMC) were examined for KSHV DNA to determine whether viral infection precedes onset of this neoplasm. Design: Randomized and blinded case–control study of prospectively collected PBMC samples from ongoing cohort studies. Methods: Paired PBMC drawn before and after KS onset from 21 AIDS-KS patients were compared to paired PBMC from 23 high-risk HIV-infected homo-/bisexual patients who did not develop KS and to a single PBMC sample from 19 low-risk, HIV-infected hemophiliac patients. Extracted DNA samples were amplified by polymerase chain reaction (PCR) using two non-overlapping nested primer sets to control for potential PCR contamination. Results: In all comparisons, patients who went on to develop KS were significantly more likely to show evidence of KSHV infection prior to onset of KS than either control group. Of PBMC samples from AIDS-KS patients drawn prior to KS, 52% were positive for KSHV DNA whereas both high- and low-risk control groups had lower rates of PBMC infection (9–13%). KSHV infection can precede KS onset by up to 21 months among AIDS-KS patients. Conclusions: AIDS-KS patients are significantly more likely to show evidence of KSHV infection in PBMC prior to KS onset than control HIV-infected patients. Because identical PBMC samples from cases and controls were examined blindly, these results are not caused by a bias in tissue sampling. Homo-/bisexual and hemophiliac AIDS patients who do not develop KS appear to have a low prevalence of infection. These findings indicate that KSHV infection is specifically associated with the subsequent development of KS in AIDS patients.

Seminal viral load is likely to be directly related to the sexual transmissibility of human immunodeficiency virus type 1 (HIV-1). However, it is not clear whether the level of HIV-1 in semen varies with the stage of infection and whether antiretroviral therapy reduces seminal viral load. A nucleic acid sequence-based amplification (NASBA) technique was used to quantify HIV-1 RNA as an indicator of infectious viral load in semen and blood plasma of homosexual men with different stages and durations of HIV-1 infection. The median viral load in a cross section of 34 men was 11,000 HIV-1 RNA copies/ml (range, <400 to 1.3 x 10(7) copies/ml) in whole semen and 5,238 HIV-1 RNA copies/ml (range, <400 to 2.8 x 10(5) copies/ml) in seminal plasma, which is 10- to 1,000-fold higher than previous estimates. Viral loads in whole semen and seminal plasma were strongly correlated with blood plasma viral load (P < 0.001) but not with blood CD4+ T-cell count (P = 0.420). Longitudinal analysis of eight subjects who progressed to AIDS showed that seminal viral load increased in most cases, with viral load consistently higher in blood plasma than in semen. Viral loads in semen and blood plasma decreased markedly in six other patients following initiation of potent combination therapy with a protease inhibitor (indinavir) and a nonnucleoside reverse transcriptase inhibitor (DMP-266). These findings have important implications for the biology of sexual transmission of HIV-1 and its potential reduction by antiretroviral therapy.

To estimate insulin resistance and its relationship to antiretroviral therapy (ART) in a cohort of HIV-infected persons with comparison to HIV-seronegative controls.Prospective cohort of 533 HIV-infected and 755 HIV-seronegative men in the Multicenter AIDS Cohort Study evaluated at 6-month intervals between 1999 and 2003.Recent ART exposure was assessed by type of treatment in the preceding 6 months [i.e., no ART, monotherapy, combination ART, or highly active antiretroviral therapy (HAART) with and without a protease inhibitor (PI)]. Cumulative exposure was determined for the three major ART classes and for individual medications within each class. Two endpoints, a modified QUICKI index, 100 x 1/[log10(glucose) + log10(insulin)] and fasting hyperinsulinemia (insulin > 15 microU/ml), were assessed. All statistical models were adjusted for age, body mass index, race, nadir CD4 cell count, hepatitis C serostatus and family history of diabetes mellitus.Each of the HIV-infected groups had higher odds of hyperinsulinemia and lower mean QUICKI than the HIV-seronegative men. Each additional year of exposure to nucleoside analogue reverse transcriptase inhibitors (NRTI) was associated with increased odds of hyperinsulinemia [odds ratio (OR), 1.08; 95% confidence interval (CI), 1.02-1.13) and a lower QUICKI (-0.04; 95% CI, -0.07 to -0.01). Cumulative exposure to non-nucleoside analogue reverse transcriptase inhibitors or PI drugs was not associated with either insulin resistance marker. Of individual medications examined, stavudine was associated with the highest risk of hyperinsulinemia (OR, 1.2; 95% CI, 1.2-1.3).Fasting surrogate markers suggest increased insulin resistance in HIV-infected men, which is related to cumulative NRTI exposure.

To estimate the time interval between human immunodeficiency virus type 1 (HIV-1) seroconversion and acquired immunodeficiency syndrome (AIDS) diagnosis in homosexual men, prospective incident cohorts are difficult to obtain and, if assembled, provide few events owing to the long incubation time. Although seroprevalent cohorts are numerous in size and events, the information is limited due to the unknown times since seroconversion. To combine the information provided by 1,628 seroprevalent men (304 AIDS cases) and 233 seroconverters (12 AIDS cases) being followed in a multicenter study since 1984, the postseroconversion changes in hematologic variables occurring in the incident cohort were used to develop a model that allowed for the imputation of the unknown times since seroconversion for the seroprevalent cohort. Nonparametric life table methods incorporating truncation and censoring were applied for the estimation of the probability distribution of the AIDS-free time after seroconversion. The precision of the estimates was evaluated using bootstrap methods. The analysis suggested that AIDS is unlikely (less than 0.5%) in the first year; 78% of seropositive homosexual men remain AIDS-free 60 months after seroconversion; and the AIDS incidence increases for months 12-36 and levels off at 38 per 1,000 person-semesters for months 42-60. The nonparametric estimate of the incidence rate suggests a median AIDS-free time of 11 years, which is longer than previous estimates based on parametric models.

Highly active antiretroviral therapy (HAART), in addition to traditional vascular risk factors, may affect coronary heart disease (CHD) risk in individuals with human immunodeficiency virus (HIV) infection.Among HIV-infected (931 men and 1455 women) and HIV-uninfected (1099 men and 576 women) adults, the predicted risk of CHD was estimated on the basis of age, sex, lipid and blood pressure levels, the presence of diabetes, and smoking status.Among HIV-infected men, 2% had moderate predicted risk of CHD (10-year CHD risk, 15%-25%), and 17% had high predicted risk (10-year CHD risk of > or = 25% or diabetes). Among HIV-infected women, 2% had moderate predicted CHD risk, and 12% had high predicted CHD risk. Compared with users of protease inhibitor-based HAART, the adjusted odds ratio (OR) for moderate-to-high risk of CHD was significantly lower among HAART-naive individuals (OR, 0.57; 95% confidence interval [CI], 0.36-0.89). Users of HAART that was not protease inhibitor based (OR, 0.74; 95% CI, 0.53-1.01) and former HAART users (OR, 0.68; 95% CI, 0.46-1.03) were also less likely than users of protease inhibitor-based HAART to have moderate-to-high CHD risk, although 95% CIs overlapped the null. Low income was associated with increased likelihood of moderate-to-high CHD risk (for annual income < $10,000 vs. > $40,000: OR, 2.32; 95% CI, 1.51-3.56 ). Elevated body mass index (calculated as weight in kilograms divided by the square of height in meters) predicted increased likelihood of moderate-to-high CHD risk (for BMI of 18.5-24.9 vs. BMI of 25-30: OR, 1.41 [95% CI, 1.03-1.93]; for BMI of 18.5-24.9 vs. BMI > or = 30: OR, 1.79 [95% CI, 1.25-2.56]).Among HIV-infected adults, in addition to antiretroviral drug exposures, being overweight and having a low income level were associated with increased predicted CHD risk. This suggests a need to target HIV-infected men and women with these characteristics for vascular risk factor screening.

The authors administered the Center for Epidemiological Studies Depression (CES-D) Scale to 4,954 homosexual men in the Multicenter AIDS Cohort Study. HIV antibody status at enrollment was a less important predictor of psychological distress than were reported physical symptoms. Multivariate analysis showed an association between a high score on each CES-D Scale component and the number of self-reported possible AIDS- or HIV-related symptoms, perceived lymphadenopathy, and absence of "someone to talk to about serious problems." This relationship between self-reported physical symptoms and psychological distress suggests a possible etiologic relationship between perceived AIDS risk and psychological symptoms in men at risk of AIDS.

Interviews regarding medical history, life-style, specific drug taking and sexual activities, and physical examinations were administered to 4,955 homosexual men who volunteered for the Multicenter AIDS Cohort Study in Baltimore, Chicago, Los Angeles, and Pittsburgh. Overall, the prevalence of antibodies to human immunodeficiency virus (HIV) in these men was 38.0%. The factor most strongly associated with prevalent HIV infection according to a multiple logistic regression model was rectal trauma, a composite variable which included receptive anal fisting, enemas before sex, reporting of blood around the rectum, and the observation of scarring, fissures or fistulas on rectal examination. Receptive anal intercourse also was strongly associated with HIV infection in the model. The multivariate relative odds for HIV antibody positivity was 7.72 for the highest level of rectal trauma and 3.04 for receptive anal intercourse. Symptoms reported to occur in some persons who subsequently develop acquired immunodeficiency syndrome (AIDS) were frequent among HIV seropositive men (12.9%) but were reported in 8.4% of seronegative men as well. Generalized lymphadenopathy was observed significantly more often in seropositive men (48.8%) compared with seronegative men (11.4%). The prevalence of HIV antibodies was inversely related to the number of T-helper cells and directly related (to a lesser extent) to the number of T-suppressor cells. The results suggest that disruption of the rectal mucosa provides access by HIV to the blood stream and to specific immunologic cells. Since symptoms and generalized lymphadenopathy were often reported among seronegative men, they probably also occur among some seropositive men not currently progressing to AIDS.

Assessment of adherence to HIV antiretroviral therapy (ART) is required for studying therapeutic effectiveness and identifying subgroups needing focused education. The study's goals were to describe the level of ART adherence using self-reported recall over a 4-day period and to characterize determinants of lower adherence. The interaction between adherence and drug holidays on level of HIV RNA also was investigated. Perfect self-reported adherence was defined as taking all doses and numbers of pills as prescribed for current HIV medications. Independent predictors of <100% adherence were determined using multivariate logistic regression. Among 539 men, 419 (77.7%) were 100% adherent by the algorithm using self-reported data. HIV-1 RNA was <50 copies/ml in 48.2% of the adherent group versus 33.7% in the less adherent group (p = .015). This proportion dropped to 28% if a drug holiday was reported in addition to lower adherence. A drug holiday was not virologically detrimental if the participant was otherwise adherent. Determinants of lower adherence included African American race (odds ratio [OR], 2.4; p = .008), income <U.S.$50,000 (OR, 2.2; p = .002), no outpatient visits (OR, 3.6; p = .003) and increasing numbers of ART medications (OR, 4.5; p = .001). These data support the validity of using a questionnaire to assess adherence in observational studies. Identification of individuals with characteristics associated with lower adherence provides the basis for interventions to enhance adherence and optimize effective therapies.

Journal Article Trends in the Incidence of Outcomes Defining Acquired Immunodeficiency Syndrome (AIDS) in the Multicenter AIDS Cohort Study: 1985–1991 Get access Alvaro Muñoz, Alvaro Muñoz 1Department of Epidemiology, The Johns Hopkins University School of Hygiene and Public HealthBaltimore, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar Lewis K. Schrager, Lewis K. Schrager 2Epidemiology Branch, Division of AIDS, National Institute of Allergy and Infectious DiseasesBethesda, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar Helena Bacellar, Helena Bacellar 1Department of Epidemiology, The Johns Hopkins University School of Hygiene and Public HealthBaltimore, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar Ilene Speizer, Ilene Speizer 1Department of Epidemiology, The Johns Hopkins University School of Hygiene and Public HealthBaltimore, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar Sten H Vermund, Sten H Vermund 2Epidemiology Branch, Division of AIDS, National Institute of Allergy and Infectious DiseasesBethesda, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar Roger Detels, Roger Detels 3Department of Epidemiology, School of Public Health, University of CaliforniaLos Angeles, Los Angeles, CA Search for other works by this author on: Oxford Academic PubMed Google Scholar Alfred J. Saah, Alfred J. Saah 1Department of Epidemiology, The Johns Hopkins University School of Hygiene and Public HealthBaltimore, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar Lawrence A. Kingsley, Lawrence A. Kingsley 4Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public HealthPittsburgh, PA Search for other works by this author on: Oxford Academic PubMed Google Scholar Daniela Seminara, Daniela Seminara 5Division of Cancer Etiology, National Cancer InstituteBethesda, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar John P. Phair John P. Phair 5Division of Cancer Etiology, National Cancer InstituteBethesda, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar American Journal of Epidemiology, Volume 137, Issue 4, 15 February 1993, Pages 423–438, https://doi.org/10.1093/oxfordjournals.aje.a116691 Published: 15 February 1993 Article history Received: 08 July 1992 Revision received: 07 December 1992 Published: 15 February 1993

Nine hundred fifty-five of 1,384 (69 per cent) gay and bisexual men enrolled in a prospective study of the natural history of human immunodeficiency virus (HIV) infection who reported engaging in anal intercourse in the past six months were surveyed about condom use practices for both insertive (IAI) and receptive anal intercourse (RAI). The following results were obtained: 23 per cent of the men reported that they always used condoms for IAI and 21 per cent for RAI; 32 per cent sometimes used condoms for IAI; 28 per cent sometimes used condoms for RAI; 45 per cent never used condoms for IAI; and 50 per cent never used condoms for RAI. Multiple logistic regression analysis revealed that the following variables were associated with both insertive and receptive condom use: condom acceptability; a history of multiple and/or anonymous partners in the past six months, and the number of partners with whom one is "high" (drugs/alcohol) during sex. Knowledge of positive HIV serostatus was more strongly associated with receptive than with insertive use. Condom use is a relatively complex health-related behavior, and condom promotion programs should not limit themselves to stressing the dangers of unprotected intercourse.

Background.Monocytes and monocyte-derived macrophages promote atherosclerosis through increased inflammation and vascular remodeling. This may be especially true in chronic human immunodeficiency virus (HIV) infection.

While 16S ribosomal RNA (rRNA) sequencing has been used to characterize the lung's bacterial microbiota in human immunodeficiency virus (HIV)-infected individuals, taxonomic studies provide limited information on bacterial function and impact on the host. Metabolic profiles can provide functional information on host-microbe interactions in the lungs. We investigated the relationship between the respiratory microbiota and metabolic profiles in the bronchoalveolar lavage fluid of HIV-infected and HIV-uninfected outpatients.Targeted sequencing of the 16S rRNA gene was used to analyze the bacterial community structure and liquid chromatography-high-resolution mass spectrometry was used to detect features in bronchoalveolar lavage fluid. Global integration of all metabolic features with microbial species was done using sparse partial least squares regression. Thirty-nine HIV-infected subjects and 20 HIV-uninfected controls without acute respiratory symptoms were enrolled. Twelve mass-to-charge ratio (m/z) features from C18 analysis were significantly different between HIV-infected individuals and controls (false discovery rate (FDR) = 0.2); another 79 features were identified by network analysis. Further metabolite analysis demonstrated that four features were significantly overrepresented in the bronchoalveolar lavage (BAL) fluid of HIV-infected individuals compared to HIV-uninfected, including cystine, two complex carbohydrates, and 3,5-dibromo-L-tyrosine. There were 231 m/z features significantly associated with peripheral blood CD4 cell counts identified using sparse partial least squares regression (sPLS) at a variable importance on projection (VIP) threshold of 2. Twenty-five percent of these 91 m/z features were associated with various microbial species. Bacteria from families Caulobacteraceae, Staphylococcaceae, Nocardioidaceae, and genus Streptococcus were associated with the greatest number of features. Glycerophospholipid and lineolate pathways correlated with these bacteria.In bronchoalveolar lavage fluid, specific metabolic profiles correlated with bacterial organisms known to play a role in the pathogenesis of pneumonia in HIV-infected individuals. These findings suggest that microbial communities and their interactions with the host may have functional metabolic impact in the lung.

Rationale and Objective Glomerular filtration rate (GFR) estimation based on creatinine and cystatin C (eGFRcr-cys) is more accurate than estimated GFR (eGFR) based on creatinine or cystatin C alone (eGFRcr or eGFRcys, respectively), but the inclusion of creatinine in eGFRcr-cys requires specification of a person’s race. β2-Microglobulin (B2M) and β-trace protein (BTP) are alternative filtration markers that appear to be less influenced by race than creatinine is. Study Design Study of diagnostic test accuracy. Setting and Participants Development in a pooled population of 7 studies with 5,017 participants with and without chronic kidney disease. External validation in a pooled population of 7 other studies with 2,245 participants. Tests Compared Panel eGFR using B2M and BTP in addition to cystatin C (3-marker panel) or creatinine and cystatin C (4-marker panel) with and without age and sex or race. Outcomes GFR measured as the urinary clearance of iothalamate, plasma clearance of iohexol, or plasma clearance of [51Cr]EDTA. Results Mean measured GFRs were 58.1 and 83.2 mL/min/1.73 m2, and the proportions of Black participants were 38.6% and 24.0%, in the development and validation populations, respectively. In development, addition of age and sex improved the performance of all equations compared with equations without age and sex, but addition of race did not further improve the performance. In validation, the 4-marker panels were more accurate than the 3-marker panels (P < 0.001). The 3-marker panel without race was more accurate than eGFRcys (percentage of estimates greater than 30% different from measured GFR [1 − P30] of 15.6% vs 17.4%; P = 0.01), and the 4-marker panel without race was as accurate as eGFRcr-cys (1 − P30 of 8.6% vs 9.4%; P = 0.2). Results were generally consistent across subgroups. Limitations No representation of participants with severe comorbid illness and from geographic areas outside of North America and Europe. Conclusions The 4-marker panel eGFR is as accurate as eGFRcr-cys without requiring specification of race. A more accurate race-free eGFR could be an important advance. Glomerular filtration rate (GFR) estimation based on creatinine and cystatin C (eGFRcr-cys) is more accurate than estimated GFR (eGFR) based on creatinine or cystatin C alone (eGFRcr or eGFRcys, respectively), but the inclusion of creatinine in eGFRcr-cys requires specification of a person’s race. β2-Microglobulin (B2M) and β-trace protein (BTP) are alternative filtration markers that appear to be less influenced by race than creatinine is. Study of diagnostic test accuracy. Development in a pooled population of 7 studies with 5,017 participants with and without chronic kidney disease. External validation in a pooled population of 7 other studies with 2,245 participants. Panel eGFR using B2M and BTP in addition to cystatin C (3-marker panel) or creatinine and cystatin C (4-marker panel) with and without age and sex or race. GFR measured as the urinary clearance of iothalamate, plasma clearance of iohexol, or plasma clearance of [51Cr]EDTA. Mean measured GFRs were 58.1 and 83.2 mL/min/1.73 m2, and the proportions of Black participants were 38.6% and 24.0%, in the development and validation populations, respectively. In development, addition of age and sex improved the performance of all equations compared with equations without age and sex, but addition of race did not further improve the performance. In validation, the 4-marker panels were more accurate than the 3-marker panels (P < 0.001). The 3-marker panel without race was more accurate than eGFRcys (percentage of estimates greater than 30% different from measured GFR [1 − P30] of 15.6% vs 17.4%; P = 0.01), and the 4-marker panel without race was as accurate as eGFRcr-cys (1 − P30 of 8.6% vs 9.4%; P = 0.2). Results were generally consistent across subgroups. No representation of participants with severe comorbid illness and from geographic areas outside of North America and Europe. The 4-marker panel eGFR is as accurate as eGFRcr-cys without requiring specification of race. A more accurate race-free eGFR could be an important advance.

To determine if the rates of malignancies other than Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL) are increased in human immunodeficiency virus (HIV)-infected homosexual men.From 1984 through 1993, 1,199 homosexual men were studied in the Pittsburgh component of the Multicenter AIDS Cohort Study (MACS), an examination of the natural history of HIV infection. The cohort consisted of 769 HIV-seronegative (SN) participants and 430 seropositive (SP) members who were either seroprevalent at the time of enrollment or who seroconverted during the study. Cancer incidence data were collected through semiannual visits, phone interviews, medical records, and death certificates. Five thousand seven hundred eight person-years and 2,344 person-years were contributed to the study by the SN and SP men, respectively.In addition to 44 cases of KS, 13 NHLs, and 3 CNS lymphomas (CNSLs), 27 other malignancies occurred (three nonmelanoma skin cancers and eight other malignancies in the SP group, eight nonmelanoma skin cancers, and eight other malignancies in the SN group). Age-adjusted rates were calculated for both groups and compared with each other and with rates for the general male population in Pennsylvania. There were no differences between the SN group and the general population. Among the SP group, the combined frequency of all cancers other than KS, NHL, CNSL, and nonmelanoma skin cancers was statistically significantly increased in comparison to both the SN group and the general population. This increase was secondary to an unusually increased frequency of both seminoma and Hodgkin's disease.These findings support the hypothesis that the incidences of cancers other than KS and lymphoma are moderately increased in the setting of HIV infection and immunosuppression.

Objective: To characterize changing survival patterns after development of clinical AIDS from 1984 to 2004, when different antiretroviral therapies were being introduced. Design: Cohort of homosexual men since 1984 and cohort of women since 1994. Methods: A total of 1504 men and 461 women were followed for all-cause mortality after an incident AIDS diagnosis. Relative hazards of death and relative times to death were determined in five therapy eras: no/monotherapy (July 1984–December 1989), monotherapy/combination therapy (January 1990–December 1994), HAART introduction (January 1995–June 1998), short-term stable HAART use (July 1998–June 2001), and moderate-term stable HAART use (July 2001–December 2003). Results: A total of 1057 (54%) study participants died. The time at which 25% of individuals died after an AIDS diagnosis increased significantly from 0.56 years [95% confidence interval (CI), 0.50–0.64] in the no/monotherapy era to 0.74 (95% CI, 0.67–0.82), 1.78 (95% CI, 1.29–2.44), 4.22 (95% CI, 2.94–6.05) and 5.08 years (95% CI, 2.39–10.79) in the four subsequent therapy eras, respectively. Inferences on the beneficial effects of HAART were confirmed after adjustment by age, sex, type of AIDS diagnosis and CD4 cell count at diagnosis. The pattern of the hazard of death after AIDS changed from increasing in the pre-HAART era to being lower and non-increasing in the eras of HAART. Conclusions: The sustained beneficial effect of HAART, even in individuals with clinical AIDS and extensive treatment histories, attenuates concerns about emergence of resistance but augurs that a substantial number of HIV-infected individuals may require care for very long periods.

We examined whether 644 homosexual men who engaged in receptive anal intercourse were at particularly elevated risk for seroconversion if they also possessed specific behavioral, health or psychosocial vulnerability characteristics. Of 11 potential factors examined, heavy drinking, moderate to heavy drug use, and younger age were significantly related to seroconversion. These variables were also associated with an increased number of sexual partners, anonymous sex, and failure to use condoms.

In this analysis the aim was to determine the independent effect of moderate to severe weight loss prior to an AIDS diagnosis on survival after AIDS. The study was conducted as part of the Multicenter AIDS Cohort Study (MACS), a longitudinal study of HIV-1-seropositive gay or bisexual men. Measured weight and self-reported weight loss data were collected semiannually from 1984 through 1993. The study population included 962 HIV-1-seropositive men who developed clinical AIDS during the follow-up period. Median survival after AIDS was significantly lower for men with measured weight loss of > or = 4.5 kg 3-9 months and 3-15 months prior to AIDS, or who had lost > 10% of their baseline body weight compared with men with less weight loss or weight gain. Men with self-reported unintentional weight loss of > or = 4.5 kg 3-9 months prior to AIDS had significantly poorer survival (median = 1.05 years vs. 1.48 years; p = 0.0001) compared with men not reporting weight loss. After adjusting for potential confounding factors, men in the high measured weight loss group 3-9 months prior to AIDS still had significantly poorer survival [relative hazard (RH) = 1.36; p = 0.02]. Similar trends were seen for the two longer intervals prior to AIDS (RH = 1.38, p = 0.01; and RH = 1.50, p = 0.02, respectively). Men who self-reported weight loss > or = 4.5 kg 3-9 months prior to AIDS also had significantly poorer survival after AIDS (RH = 1.43; p = 0.002) in multivariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: The relationships between frailty and body composition in older adults with HIV infection are poorly understood. We sought to describe associations between frailty and measures of body composition among adult men with HIV and without HIV. Design/Methods: Men with and without HIV (age 50–69 years) in the Multicenter AIDS Cohort Study (MACS) Bone Strength Substudy were included if evaluated for frailty (by Fried phenotype) and body composition [BMI, waist circumference, abdominal visceral (VAT) and subcutaneous (SAT) adipose tissue, sarcopenia, and osteopenia/osteoporosis]. All participants with HIV infection were on antiretroviral therapy. Multivariate multinomial logistic regression models were used to determine associations of frailty with body composition. Results: A total of 399 men, including 199 men with HIV and 200 men without HIV, both with median age 60 years, constituted our study population. Frailty prevalence was 16% (men with HIV) vs. 8% (men without HIV). HIV serostatus was associated with a 2.43 times higher odds of frailty (P = 0.01). Higher waist circumference, VAT, sarcopenia, and femoral neck osteoporosis were associated with increased odds of frailty (aOR 4.18, 4.45, 4.15, and 13.6, respectively, and all P < 0.05); BMI and SAT were not. None of these measures presented a differential association with frailty by HIV serostatus (all P > 0.20). Conclusion: Higher abdominal obesity and sarcopenia were associated with frailty among men with and without HIV. Assessment of these body composition parameters may help detect frailty in the clinical setting.

Human immunodeficiency virus (HIV) infection is associated with pulmonary disease and worse lung function, but the relationship of lung function with survival in HIV is unknown.To determine whether lung function is associated with all-cause mortality in HIV-infected individuals.HIV-infected participants from cohorts in three locations underwent pre- and post-bronchodilator spirometry and determination of single-breath diffusing capacity of the lung for carbon monoxide (DlCO) in 2008-2009, computed tomographic (CT) scanning of the chest for quantitative emphysema and airway measures, and echocardiography for estimated left ventricular systolic and diastolic function and tricuspid regurgitant velocity. Bivariate analysis and multivariable Cox proportional hazards models were used to determine whether decreased lung function was independently associated with increased all-cause mortality. Models were adjusted for covariates including age, sex, body mass index, smoking status, self-reported hepatitis C status, HIV viral levels, CD4+ T-cell counts, hemoglobin, antiretroviral therapy, and illicit drug use.Overall, 396 HIV-infected participants underwent pulmonary function testing. Thirty-two participants (8%) died during a median follow-up period of 69 months. A post-bronchodilator FEV1-to-FVC ratio less than 0.7 (hazard ratio [HR], 2.47; 95% confidence interval [CI], 1.10-5.58) and a DlCO less than 60% (HR, 2.28; 95% CI, 1.08-4.82) were independently associated with worse mortality. Also, hepatitis C (HR, 2.68; 95% CI, 1.22-5.89) and baseline plasma HIV RNA level (HR per ln RNA copies/ml, 1.50; 95% CI, 1.22-1.86) were associated with mortality in HIV-infected participants. The only CT or echocardiographic measure associated with greater mortality in univariate analysis was greater wall thickness of medium-sized airways (HR for wall area percent, 1.08; 95% CI, 1.00-1.18; P = 0.051), but none of the CT or echocardiogram measures were associated with mortality in multivariable analysis.Airflow obstruction and impaired diffusing capacity appear to be associated with all-cause mortality in HIV-infected persons over an average of 6 years of follow-up. These data highlight the importance of lung dysfunction in HIV-infected persons and should be confirmed in larger cohorts and with extended follow-up periods. Clinical trial registered with www.clinicaltrials.gov (NCT00869544, NCT01326572).

Higher white blood cell counts in smokers compared with nonsmokers have been well documented, but the longitudinal relation between changes in smoking and changes in white blood cells has not been well described. Since 1984, data have been collected semiannually by the Multicenter AIDS Cohort Study (MACS), a four-center prospective cohort study of acquired immunodeficiency syndrome (AIDS) in homosexual men. The study population includes 2,435 participants who were human immunodeficiency virus (HIV) seronegative as of September 1994 and who contributed 20,918 person-visits for this analysis. For individuals who modified their smoking behavior, changes in white blood cell counts occurred primarily during the first 6 months following changes in the amount of cigarettes smoked. Among former smokers who resumed smoking, the extent of the increase in white blood cell count depended on the number of cigarettes smoked. Specifically, increases of 241, 340, and 740 cells/μliter were observed for smokers who resumed smoking ±1, 1 to ±2, and >2 packs/day, respectively. Conversely, smokers who quit smoking had a decrease of white blood cell count: −32, −629, and −1,122 cells/μliter for men who previously smoked ±1, 1 to ±2, and >2 packs/day, respectively. Long-term ex-smokers, however, still had higher white blood cell counts than did never smokers. There was a high within-individual correlation of white blood cell count in persons who reported a consistent level of smoking (i.e., average correlations between two white blood cell counts 6 years apart were 0.51 for never smokers, 0.48 for ex-smokers, 0.56 for men who smoked ±1 pack/day, and 0.43 for men who smoked >1 pack/day). These analyses indicate an acute effect of changes in smoking on changes in white blood cell count, a residual effect of having been a smoker, and high long-term tracking for white blood cell count. Am J Epidemiol 1996; 144: 734–41.

This study evaluates two AIDS risk-reduction interventions targeted at homosexual and bisexual men. Participants were randomized into two peer-led interventions: both involved a lecture on ‘safer sex’, and one provided a skills-training component during which men could discuss and rehearse the negotiation of safer sexual encounters. Follow-up data collection assessed self-reported changes in sexual behavior at 6 and 12 months. Skills training increased condom use for insertive anal intercourse. In sessions providing skills training, condom use increased, on average, by 44% between pre-test and second follow-up compared with only 11% on average in sessions which did not provide such training.

The rate of disease progression varies considerably among human immunodeficiency virus type 1 (HIV-1)-infected individuals. Several cross-sectional studies have shown an association between the stage of HIV-1 disease and the viral burden or the relative levels of viral gene expression. To study the extent of HIV-1 transcription and replication and its correlations with disease progression, we quantified serial, longitudinal samples of blood cells from 10 HIV-1-infected individuals with markedly different rates of CD4+ T-cell number decline following seroconversion. After normalization for the input nucleic acid content, multiply spliced viral mRNA and unspliced viral RNA were quantified by competitive reverse transcription-PCR using oligonucleotide primers which flank the major tat/rev/nef splice junction and span an internal region of the gag open reading frame, respectively. Coamplification of internal cRNA template controls was used to normalize for variation in the efficiency of reverse transcription and in vitro enzymatic amplification. Similarly, proviral DNA was also quantified by competitive PCR performed within the linear range of amplification. Viral RNA was detected in the blood cells of each individual from all time points regardless of the rate of CD4+ T-cell decline. Unspliced genomic viral RNA rapidly increased in the blood cells from HIV-1-infected individuals who had a precipitously declining CD4+ T-cell number. In contrast, both unspliced and multiply spliced viral mRNAs remained relatively stable in the blood cells from HIV-1-infected individuals who have had a relatively benign clinical course. These data demonstrate that the extent of viral transcription and replication correlates with the rate of CD4+ T-cell number decline and that quantifying intracellular viral RNA is of potential prognostic value.

There is limited evidence that among HIV-infected patients haemoglobin A1c (HbA1c) values may not accurately reflect glycaemia. We assessed HbA1c discordance (observed HbA1c - expected HbA1c) and associated factors among HIV-infected participants in the Multicenter AIDS Cohort Study (MACS).Fasting glucose (FG) and HbA1c were measured at each semi-annual MACS visit since 1999. All HIV-infected and HIV-uninfected men for whom at least one FG and HbA1c pair measurement was available were evaluated. Univariate median regression determined the association between HbA1c and FG by HIV serostatus. The relationship between HbA1c and FG in HIV-uninfected men was used to determine the expected HbA1c. Generalized estimating equations determined factors associated with the Hb1Ac discordance among HIV-infected men. Clinically significant discordance was defined as observed HbA1c - expected HbA1c ≤-0.5%.Over 13 years, 1500 HIV-uninfected and 1357 HIV-infected men were included, with a median of 11 visits for each participant. At an FG of 125 mg/dL, the median HbA1c among HIV-infected men was 0.21% lower than among HIV-uninfected men and the magnitude of this effect increased with FG >126 mg/dL. Sixty-three percent of HIV-infected men had at least one visit with clinically significant HbA1c discordance, which was independently associated with: low CD4 cell count (<500 cells/mm(3)); a regimen containing a protease inhibitor, a non-nucleoside reverse transcriptase inhibitor or zidovudine; high mean corpuscular volume; and abnormal corpuscular haemoglobin.HbA1c underestimates glycaemia in HIV-infected patients and its use in patients with risk factors for HbA1c discordance may lead to under-diagnosis and to under-treatment of established diabetes mellitus.

Several lung diseases are increasingly recognized as comorbidities with HIV; however, few data exist related to the spectrum of respiratory symptoms, diagnostic testing, and diagnoses in the current HIV era. The objective of the study is to determine the impact of HIV on prevalence and incidence of respiratory disease in the current era of effective antiretroviral treatment. A pulmonary-specific questionnaire was administered yearly for three years to participants in the Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS). Adjusted prevalence ratios for respiratory symptoms, testing, or diagnoses and adjusted incidence rate ratios for diagnoses in HIV-infected compared to HIV-uninfected participants were determined. Risk factors for outcomes in HIV-infected individuals were modeled. Baseline pulmonary questionnaires were completed by 907 HIV-infected and 989 HIV-uninfected participants in the MACS cohort and by 1405 HIV-infected and 571 HIV-uninfected participants in the WIHS cohort. In MACS, dyspnea, cough, wheezing, sleep apnea, and incident chronic obstructive pulmonary disease (COPD) were more common in HIV-infected participants. In WIHS, wheezing and sleep apnea were more common in HIV-infected participants. Smoking (MACS and WIHS) and greater body mass index (WIHS) were associated with more respiratory symptoms and diagnoses. While sputum studies, bronchoscopies, and chest computed tomography scans were more likely to be performed in HIV-infected participants, pulmonary function tests were no more common in HIV-infected individuals. Respiratory symptoms in HIV-infected individuals were associated with history of pneumonia, cardiovascular disease, or use of HAART. A diagnosis of asthma or COPD was associated with previous pneumonia. In these two cohorts, HIV is an independent risk factor for several respiratory symptoms and pulmonary diseases including COPD and sleep apnea. Despite a higher prevalence of chronic respiratory symptoms, testing for non-infectious respiratory diseases may be underutilized in the HIV-infected population.

Background HIV-infected persons have an increased risk of atherosclerosis relative to uninfected individuals. Inflammatory processes may contribute to this risk. We evaluated the associations of 10 biomarkers of systemic inflammation (CRP, IL-6, sTNF-αR1 and 2), monocyte activation (CCL2, sCD163, sCD14), coagulation (fibrinogen, D-dimer), and endothelial dysfunction (ICAM-1) with subclinical carotid atherosclerosis among participants in the Multicenter AIDS Cohort Study (MACS). Methods Carotid plaque and intima media thickness (IMT) in the common carotid (CCA-IMT) and bifurcation region were assessed by B mode ultrasound among 452 HIV-infected and 276 HIV-uninfected men from 2010–2013. Associations between levels of each biomarker and presence of focal plaque and IMT were assessed by logistic and linear regression models, adjusting for demographics, risk behaviors, traditional cardiovascular disease (CVD) risk factors, and HIV disease characteristics. Results Compared to HIV-uninfected men, HIV-infected men had significantly higher levels of 8 of the 10 biomarkers. Overall, men with sCD163, CCL2, IL-6, and CRP levels in the highest quintile had approximately 2 times the odds of carotid plaque relative to those with levels in the lowest quintile, independent of demographic and CVD risk factors. Fibrinogen levels were positively associated with CCA-IMT while ICAM-1, CCL2, and sTNF-αR1 levels were positively associated with bifurcation-IMT. Among HIV-uninfected men, higher levels of sTNF-αR2 were positively associated with CCA-IMT, fibrinogen with bifurcation-IMT and carotid plaque, and ICAM-1 with carotid plaque. Conclusion In addition to greater levels of systemic inflammation, heightened monocyte activation (sCD163, CCL2) may contribute to the burden of atherosclerosis among HIV-infected persons.

The extent to which inflammation, immune activation/immunosenescence, and hormonal abnormalities are driven by human immunodeficiency virus (HIV) or frailty is not clear.HIV-infected frail men (n = 155) were matched to nonfrail, HIV-infected (n = 141) and HIV-uninfected (n = 150) men by age, calendar year, and antiretroviral therapy use (HIV-infected men only). Frailty was defined by ≥3 frailty-related phenotype criteria (weight loss, exhaustion, low activity, slowness) at ≥2 visits, or at 1 visit with ≥1 criteria at ≥2 visits. The following measurements were obtained: interleukin 6, high-sensitivity C-reactive protein, soluble receptors for tumor necrosis factor α 1 and 2, the percentages of CD4+CD28-, CD8+CD28-, CD4+CD38+HLA-DR+, and CD8+CD38+HLA-DR+ T cells, dehydroepiandrosterone sulfate, free testosterone, homeostatic model assessment of insulin resistance, and insulin-like growth factor 1. Log-linear regressions were adjusted for a priori selected covariates to determine differences by frailty and HIV status.In multivariate analyses adjusted for covariates, frailty was associated among HIV-infected men with higher interleukin 6 and high-sensitivity C-reactive protein and lower free testosterone and dehydroepiandrosterone levels. In contrast, HIV infection but not frailty was associated with significantly greater immune senescence (percentage of CD4+CD28- or CD8+CD28- T cells) and immune activation (percentages of CD4+CD38+HLA-DR+ and CD8+CD38+HLA-DR+ T cells).Frailty among HIV-infected men was associated with increased inflammation and lower hormone levels, independent of comorbid conditions. Interventions targeting these pathways should be evaluated to determine the impact on prevention or reversal of frailty among HIV-infected men.

Background: Falls and fall risk factors are common among people living with HIV (PLWH). We sought to identify fall risk factors among men with and without HIV. Methods: Men aged 50–75 years with (n = 279) and without HIV (n = 379) from the Bone Strength Substudy of the Multicenter AIDS Cohort Study were included. Multinomial logistic regression models identified risk factors associated with falling. Results: One hundred fourteen (41%) PLWH and 149 (39%) of uninfected men had ≥1 fall; 54 (20%) PLWH and 66 (17%) of uninfected men experienced ≥2 falls over 2 years. Five and 3% of PLWH and uninfected men, respectively, had a fall-related fracture ( P = 0.34). In multivariate models, the odds of ≥2 falls were greater among men reporting illicit drug use, taking diabetes or depression medications, and with peripheral neuropathy; obesity was associated with a lower risk (all P &lt; 0.05). In models restricted to PLWH, detectable plasma HIV-1 RNA, current use of efavirenz or diabetes medications, illicit drug use, and peripheral neuropathy were associated with greater odds of having ≥2 falls ( P &lt; 0.05). Current efavirenz use was associated with increased odds of an injurious fall; longer duration of antiretroviral therapy was protective (both P &lt; 0.05). Greater physical activity was associated with lower risk of falls with fracture ( P &lt; 0.05). Conclusions: Identified risk factors for recurrent falls or fall with fracture included low physical activity, detectable HIV-1 RNA, use of efavirenz, or use of medications to treat diabetes and depression. Fall risk reduction should prioritize interventions targeting modifiable risk factors including increased physical activity, antiretroviral therapy adherence, and transition off efavirenz.

<h3>Objective</h3> To compare the postoperative course and complications after tonsillectomy or tonsillectomy and adenoidectomy in children with Down syndrome (group 1) with the postoperative course and complications in children in a control group (group 2). <h3>Design</h3> Retrospective review of medical records for the period January 1, 1986, through March 30, 1996. <h3>Setting</h3> Tertiary care children's hospital. <h3>Patients</h3> The study included 87 children in group 1 and 64 children in group 2 matched for age, sex, and year of surgery. <h3>Intervention</h3> Tonsillectomy and adenoidectomy(group 1, 79 children; group 2, 57 children) and tonsillectomy (group 1, 8 children; group 2, 7 children). <h3>Main Outcome Measures</h3> Length of hospitalization and postoperative complications. <h3>Results</h3> The length of hospitalization was significantly increased for the children in group 1 compared with that of children in group 2 (1.6 vs 0.80 days;<i>P</i>=.001, Mann-Whitney<i>U</i>test). Twenty-two children (25%) in group 1 required airway management or observation in the pediatric intensive care unit compared with no children in group 2 who required such care (<i>P</i>&lt;.001, Fisher exact test). None of the children in either group required reintubation, continuous positive airway pressure, or tracheotomy. Respiratory complications requiring intervention were 5 times more likely in group 1 (22 [25] vs 3 [5];<i>P</i>&lt;.001, Fisher exact test). The median time until intake of clear liquids and duration of intravenous therapy were significantly increased in group 1 compared with group 2 (5.0 vs 4.0 hours,<i>P</i>=.03; 23.5 vs 16.0 hours,<i>P</i>=.001, respectively; Mann-Whitney<i>U</i>test). <h3>Conclusions</h3> Although tonsillectomy and adenoidectomy can be performed safely in children with Down syndrome, the rate of postoperative respiratory complications is higher and the duration until adequate oral intake is resumed is longer. We therefore recommend that children with Down syndrome be admitted to the hospital overnight after undergoing tonsillectomy and adenoidectomy.

In a prospective cohort of 2,647 human immunodeficiency virus type 1 (HIV-1) seropositive homosexual men enrolled in Baltimore, Chicago, Los Angeles, and Pittsburgh, 891 developed clinical acquired immunodeficiency syndrome (AIDS) between June 1984 and January 1992. Cox proportional hazards models were used to examine temporal trends in survival after AIDS for specific diagnoses, controlling for level of immunosuppression at diagnosis, age, race, and geographic location. Median survival time following AIDS onset increased from 11.6 months in 1984–1985 to 19.5 months in 1988–1989; for those diagnosed in 1990–1991, the median survival time dropped to 17.2 months. Trends in improved survival were diagnosis-specific. Survival after Pneumo-cystis carinii pneumonia consistently improved from 1984 to 1991 (p < 0.001). Compared with men diagnosed in 1984–1985, those diagnosed with p. carinii pneumonia in 1990–1991 had one-tenth the hazard of dying. For men with > 100 helper T-lymphocytes (CD4+ cells) when diagnosed with Kaposi's sarcoma, the relative hazards (95% confidence intervals) of dying after Kaposi's sarcoma were 0.8 (0.42–1.60) in 1986–1987, 0.7 (0.34–1.58) in 1988–1989, and 0.6 (0.19–1.61) in 1990–1991 compared with those diagnosed before 1986. Men with <100 CD4+ cells when diagnosed with Kaposi's sarcoma did not demonstrate a consistent change in their subsequent survival. After a nonsignificant (p < 0.05) initial improvement in prognosis, there has not been a significant improvement in survival for men who presented with other opportunistic infections. Observed increases in overall survival probably relate to improved treatment of patients who develop P. carinii pneumonia. Limited improvement in survival following other AIDS diagnoses indicates the need for developing effective treatment against these diseases.

Journal Article Temporal Trends in Human Immunodeficiency Virus type 1 Seroconversion 1984–1989: A Report from the Multicenter AIDS Cohort Study (MACS) Get access Lawrence A. Kingsley, Lawrence A. Kingsley 1Departments of Infectious Diseases and Microbiology/Epidemiology, Graduate School of Public Health, University of PittsburghPittsburgh, PA Reprint requests to Dr. Lawrence A. Kingsley, Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, 130 Desoto Street, A417 Crabtree Hall, Pittsburgh, PA 15261. Search for other works by this author on: Oxford Academic PubMed Google Scholar Susan Y. J. Zhou, Susan Y. J. Zhou 1Departments of Infectious Diseases and Microbiology/Epidemiology, Graduate School of Public Health, University of PittsburghPittsburgh, PA Search for other works by this author on: Oxford Academic PubMed Google Scholar Helena Bacellar, Helena Bacellar 2Department of Epidemiology, The Johns Hopkins University School of Public HealthBaltimore, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar Charles R. Rinaldo, Jr., Charles R. Rinaldo, Jr. 1Departments of Infectious Diseases and Microbiology/Epidemiology, Graduate School of Public Health, University of PittsburghPittsburgh, PA Search for other works by this author on: Oxford Academic PubMed Google Scholar Joan Chmiel, Joan Chmiel 3Cancer Center Biometry Section, Northwestern University Medical SchoolChicago, IL Search for other works by this author on: Oxford Academic PubMed Google Scholar Roger Detels, Roger Detels 4Department of Epidemiology, School of Public Health, University of CaliforniaLos Angeles, CA Search for other works by this author on: Oxford Academic PubMed Google Scholar Alfred Saah, Alfred Saah 2Department of Epidemiology, The Johns Hopkins University School of Public HealthBaltimore, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar Mark VanRaden, Mark VanRaden 5National Institute of Allergy and Infectious DiseasesBethesda, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar Monto Ho, Monto Ho 1Departments of Infectious Diseases and Microbiology/Epidemiology, Graduate School of Public Health, University of PittsburghPittsburgh, PA Search for other works by this author on: Oxford Academic PubMed Google Scholar Alvaro Muñoz, Alvaro Muñoz 2Department of Epidemiology, The Johns Hopkins University School of Public HealthBaltimore, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar ... Show more Multicenter AIDS Cohort Study Group Multicenter AIDS Cohort Study Group Search for other works by this author on: Oxford Academic PubMed Google Scholar American Journal of Epidemiology, Volume 134, Issue 4, 15 August 1991, Pages 331–339, https://doi.org/10.1093/oxfordjournals.aje.a116094 Published: 15 August 1991 Article history Received: 08 February 1991 Revision received: 24 April 1991 Published: 15 August 1991

Only one fifth or fewer of the female sexual partners of HIV-1-infected men with hemophilia become infected. The risk factors associated with heterosexual transmission of HIV-1 are not well understood. To investigate the hypothesis that HIV-1 viral load may be related to heterosexual HIV-1 transmission, we measured HIV-1 RNA by polymerase chain reaction (PCR) in frozen samples from 39 men with hemophilia and HIV-1 infection obtained between 20 and 62 months after HIV-1 seroconversion, during at least a 6-month relationship with a female sexual partner. The median time from the hemophilic viral load determination to the estimated date of transmission to the female partner was 9 months (range, 4-41 months). The proportion of HIV-positive hemophilic men with >100,000 HIV RNA copies/ml was significantly higher in transmitters (TR) (3 of 5 [60%]), than in nontransmitters (NTR) (3 of 34 [9%]; p = 0.027). There were no differences between TR and NTR in age at seroconversion (32.4 years each), in time from seroconversion to AIDS (67 versus 79 months), in mean CD4 number (245/microl] versus 260/microl); nor in the proportion who developed AIDS (4 of 5 [80%] versus 24 of 34 [71%]). These findings appear to suggest that high HIV viral load in HIV-infected hemophilic men increases the risk of HIV transmission to heterosexual partners. Viral load determinations may be helpful in counseling hemophilic couples regarding transmission to female partners.

A cohort of 2915 HIV-1-seronegative men from the four centers of the Multicenter AIDS Cohort Study (MACS) was followed at 6 month intervals for 24 months to identify men who developed antibodies to HIV-1. Two hundred thirty-two men (8%) seroconverted. The highest attack rate was among men who reported practicing both receptive and insertive anal-genital intercourse. The attack rate among men who reported practicing receptive but not insertive intercourse was 3.6 times higher than among men practicing insertive intercourse although those practicing insertive only reported 38% more different partners. Only two men seroconverted who reported not practicing analgenital intercourse in the 12 month prior to the first antibody-positive visit. Because men were followed every 6 months, one of these men could have been infected within 6 months of the actual development of HIV-1 antibodies. The seroconversion rate was significantly lower among men who reported using condoms with all their partners. The results of this study (a) reaffirm that receptive anal-genital intercourse is the major route of infection among homosexual men of HIV-1, (b) suggest that there is a low risk of HIV-1 infection to the insertive partner in anal-genital intercourse, (c) suggest that infection may rarely occur through sexual activities other than anal-genital intercourse, (d) provide evidence that condoms as currently used by men in the MACS provide significant but not complete protection against HIV-1 infection, and (e) suggest that the number of men in the homosexual community engaging in high-risk behavior is declining.

This study evaluates two AIDS risk-reduction interventions targeted at homosexual and bisexual men. Participants were randomized into two peer-led interventions: both involved a lecture on ‘safer sex’, and one provided a skills-training component during which men could discuss and rehearse the negotiation of safer sexual encounters. Follow-up data collection assessed self-reported changes in sexual behavior at 6 and 12 months. Skills training increased condom use for insertive anal intercourse. In sessions providing skills training, condom use increased, on average, by 44% between pre-test and second follow-up compared with only 11% on average in sessions which did not provide such training.

A study was performed to determine the relationship between level of long-term antecedent diabetic control and early diabetic retinopathy changes. Fifty-eight insulin dependent diabetics aged 14 to 17 1/2 years, with duration of diabetes of at least 8 years, were studied. Glycosylated hemoglobins were assessed a mean of 8.5 times per patient, over a mean period of 3.1 years, representing 28% of the mean duration of diabetes in this patient population. Fluorescein angiography, obtained according to a standardized technique, was assessed in masked fashion for number of microaneurysms, presence of abnormal areas of capillary nonperfusion, and presence of intraretinal dye leakage. Sixty-four percent of the study population showed some evidence of retinopathy. There was a high correlation found between degree of metabolic control as measured by glycosylated hemoglobin level, and presence of early retinopathy changes as defined by angiography.

Objective HIV-infected (HIV+) individuals may be at increased risk for sudden arrhythmic cardiac death. Some studies have reported an association between HIV infection and prolongation of the electrocardiographic QT interval, a measure of ventricular repolarisation, which could potentiate ventricular arrhythmias. We aimed to assess whether HIV+ men have longer QT intervals than HIV-uninfected (HIV−) men and to determine factors associated with QT duration. Methods We performed resting 12-lead ECGs in 774 HIV+ and 652 HIV− men in the Multicenter AIDS Cohort Study (MACS). We used multivariable linear and logistic regression analyses to assess associations between HIV serostatus and Framingham corrected QT interval (QTc), after accounting for potential confounders. We also determined associations among QTc interval and HIV-related factors in HIV+ men. In a subgroup of participants, levels of serum markers of inflammation were also assessed. Results After adjusting for demographics and risk factors, QTc was 4.0 ms longer in HIV+ than HIV− men (p&lt;0.001). Use of antiretroviral therapy (ART), specific ART drug class use and other HIV-specific risk factors were not associated with longer QTc. Among the subgroup with inflammatory biomarker measurements, higher interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and B-cell activating factor levels were independently associated with longer QTc and their inclusion partially attenuated the HIV effect. Conclusions HIV+ men had longer QTc, which was associated with higher levels of systemic inflammatory factors. This longer QTc may contribute to the increased risk for sudden arrhythmic cardiac death in some HIV+ individuals.

The objective of this study was to determine if clinical signs, symptoms, laboratory variables, and use of therapeutic or prophylactic agents have prognostic associations with survival after diagnosis of clinical AIDS. A total of 2,168 homosexual men, seropositive for human immunodeficiency virus type 1 (HIV-1) participated in a longitudinal cohort study of the greater metropolitan areas of Baltimore, Maryland, Washington, D.C., Chicago, Illinois, Pittsburgh, Pennsylvania, and Los Angeles, California, U.S.A.--the Multicenter AIDS Cohort Study (MACS). Variables within 6 months prior to AIDS diagnosis included age, CD4+ lymphocyte counts, hemoglobin, and self-reported thrush, fever, anti-retroviral therapy (ART) beginning prior to AIDS onset, and ART beginning after AIDS (as a time-dependent covariate) were analyzed as mutually exclusive categories, as was prophylaxis for Pneumocystis carinii pneumonia (PCP). Univariate and multivariate survival models of time from AIDS to death were fit. In univariate analysis, younger age, higher counts of CD4+ lymphocytes, hemoglobin, and absence of thrush or fever prior to AIDS onset were associated with longer survival after AIDS. Those who began ART within 3 months after AIDS onset had longer median survival (1.75 years), from 3 months after AIDS, when compared with those who began ART prior to AIDS (1.18 years). This comparison is not influenced by the bias that those who survive longer have a greater likelihood to subsequently receive ART. Prophylaxis for PCP beginning after AIDS onset was also associated with longer post-AIDS survival when compared with beginning prophylaxis prior to AIDS or never using prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine whether the excess prevalence of human immunodeficiency virus type 1 (HIV-1) infection in US black and Hispanic homosexual men relative to white men can be explained by differences in sociodemographic factors, history of sexually transmitted diseases, or sexual and drug-use behaviors, the authors conducted a cross-sectional analysis of baseline HIV-1 seroprevalence and HIV-1 risk factors among 4,475 non-Hispanic white, 234 Hispanic white, and 194 black homosexual men from four centers in the United States (Baltimore/Washington, DC, Pittsburgh, Chicago, and Los Angeles). HIV-1 seroprevalence was significantly higher in Hispanic men (50%; odds ratio (OR) = 1.83, 95% confidence interval (CI) 1.41-2.39) and black men (47%; OR = 1.62, 95% CI 1.21-2.16) compared with white men (35%). Both Hispanic and black men more frequently reported a history of sexually transmitted diseases. Overall, Hispanics had the highest risk profile and blacks the lowest risk profile with respect to certain high-risk sexual behaviors (e.g., receptive anal intercourse and use of anonymous sexual partners) and recreational drug use. After multivariate adjustment, black race remained a significant independent risk factor for HIV-1 seropositivity (OR = 1.60, 95% CI 1.13-2.26), but Hispanic ethnicity was no longer statistically significant (OR = 1.17, 95% CI 0.82-1.69). Most of the excess HIV-1 prevalent infection among Hispanics was explained by their predominant recruitment from Los Angeles--the study center with the highest HIV-1 seroprevalence--and their greater prevalence of a history of sexually transmitted diseases and certain high-risk sexual practices. By contrast, adjustment for these same risk behaviors failed to explain the observed black-white differences in HIV-1 seroprevalence, and further studies are needed to elucidate the reasons for these unexplained racial differences. HIV-1 educational programs for homosexual men should take into account the behavioral differences that exist between white and minority racial/ethnic groups.

Gupta, P.*; Singh, M. K.*; Rinaldo, C.*§; Ding, M.*; Farzadegan, H.†; Saah, A.†; Hoover, D.†; Moore, P.†; Kingsley, L.*¶ Author Information

Objective: Among people with HIV, there are few long-term studies of noninvasive ultrasound-based measurements of the carotid artery predicting major health events. We hypothesized that such measurements are associated with 10-year mortality in the Women's Interagency HIV Study (WIHS) and Multicenter AIDS Cohort Study (MACS), and that associations differ by HIV serostatus. Design: Nested cohort study. Methods: Participants without coronary heart disease underwent B-mode carotid artery ultrasound, with measurement of common carotid artery intima–media thickness (IMT); carotid artery plaque (focal IMT > 1.5 mm) at six locations; and Young's modulus of elasticity, a measure of arterial stiffness. We examined all-cause mortality using Cox models, controlling for demographic, behavioral, cardiometabolic, and HIV-related factors. Results: Among 1722 women (median age 40 years, 90% nonwhite, 71% HIV-positive) and 1304 men (median age 50, 39% nonwhite, 62% HIV-positive), 11% died during follow-up. Mortality was higher among HIV-positive women [19.9 deaths/1000 person-years, 95% confidence interval (CI) 14.7–28.8] than HIV-positive men (15.1/1000, 95% CI 8.3–26.8). In adjusted analyses, plaque was associated with mortality (hazard ratio 1.44, 95% CI 1.10–1.88) regardless of HIV serostatus, and varied by sex (among women, hazard ratio 1.06, 95% CI 0.74–1.52; among men; hazard ratio 2.19, 95% CI 1.41–3.43). The association of plaque with mortality was more pronounced among HIV-negative (hazard ratio 3.87, 95% 1.95–7.66) than HIV-positive participants (hazard ratio 1.35, 95% CI 1.00–1.84). Arterial stiffness was also associated with mortality (hazard ratio 1.43 for highest versus lowest quartile, 95% CI 1.02–2.01). Greater common carotid artery-IMT was not associated with mortality. Conclusion: Carotid artery plaque was predictive of mortality, with differences observed by sex and HIV serostatus.

<h2>Abstract</h2><h3>Background and aims</h3> People living with HIV (HIV+) are surviving longer due to effective antiretroviral therapy. Cardiovascular disease is a leading cause of non-AIDS related clinical events. We determined HIV-related factors associated with coronary artery stenosis progression. <h3>Methods</h3> We performed serial coronary CT angiography among HIV+ and HIV-uninfected (HIV-) men in the Multicenter AIDS Cohort Study. The median inter-scan interval was 4.5 years. Stenosis was graded as 0, 1–29, 30-49, 50–69 or ≥70%. Progression was defined as an increase ≥2 categories. Suppressed HIV infection was consistent viral loads <50 copies/mL allowing 1 "blip" <500 copies/mL, otherwise considered viremic. Multivariable Poisson regression analysis assessed adjusted associations between HIV serostatus and viremia with coronary stenosis progression. <h3>Results</h3> The sample included 310 HIV+ (31% viremic) and 234 HIV- men. The median age was 53 years, 30% Black and 23% current smokers. Viremic men were 2.3 times more likely to develop coronary stenosis progression than HIV- men (adjusted RR 2.30; 95% CI, 1.32–4.00, <i>p</i> = 0.003), with no difference in progression between HIV+ suppressed and HIV- men (RR 1.10; 95% CI, 0.70–1.74, <i>p</i> = 0.67). There was a progressive increase in adjusted relative risk with greater viremia (<i>p</i> = 0.03). Men with >1 viral load >500 copies/ml demonstrated greatest stenosis progression (RR 3.01; 95% CI, 1.53–4.92, <i>p</i> = 0.001 compared with HIV- men). Suppressed HIV+ men with suboptimal antiretroviral adherence had greater stenosis progression (RR 1.91; 95% CI 1.12–3.24, <i>p</i> = 0.02) than HIV + suppressed men with optimal adherence. <h3>Conclusions</h3> Coronary artery stenosis progression was associated with suboptimal HIV RNA suppression and antiretroviral therapy adherence. Effective ongoing HIV virologic suppression and antiretroviral therapy adherence may mitigate risk for coronary disease events among people living with HIV.

To review the effectiveness of a perioperative management protocol and our experience with a large population of patients with von Willebrand disease (vWD) who require adenotonsillar surgery (T&A).A retrospective review of the medical records of all patients having the diagnosis of vWD who underwent T&A between January 1, 1992, and July 31, 1996.A tertiary care, university-based children's hospital.Patients having a preoperative diagnosis of vWD received a single intravenous dose of desmopressin acetate, 0.3 pg/kg, approximately 20 minutes before the induction of anesthesia. Beginning January 15, 1994, a standard management protocol involving the postoperative administration of fluids and electrolytes was followed.Operative blood loss and the incidence of postoperative bleeding and of hyponatremia.Of approximately 4800 patients who underwent T&A during the study period, 69 patients had a diagnosis of vWD. All 67 patients identified preoperatively received desmopressin; 2 were identified by postoperative workup as a result of excessive surgical bleeding. Minimal immediate postoperative bleeding was noted in 7 patients (10%), but none required intervention. Delayed bleeding occurred in 9 patients (13%); all were readmitted to the hospital for observation, 4 (6%) requiring operative cauterization. Substantial postoperative hyponatremia occurred in 3 patients, and 1 patient had seizure activity. Symptomatic hyponatremia has been avoided since a protocol of fluid and electrolyte administration was instituted.Although T&A can be performed safely in patients with vWD, it is not without an increased risk of postoperative hemorrhage. The administration of desmopressin has been reported to reduce the risk of bleeding, but it is not without risk. A protocol for fluid and electrolyte management is recommended.

T cell immunity to lytic proteins of herpesviruses is important in host control of infection. We have characterized the cytotoxic T lymphocyte (CTL) response to 5 human herpesvirus 8 (HHV-8) homologues of lytic proteins in HHV-8—seropositive individuals. HLA class I—restricted, CD8+ CTL responses to ⩽ 1 HHV-8 lytic protein were detected in all 14 HHV-8—seropositive study subjects tested, with or without human immunodeficiency virus type 1 (HIV-1) infection, but not in any of 5 HHV-8—seronegative individuals. Seven of these study subjects with both HHV-8 and HIV-1 infection had greater anti-CTL reactivity to glycoprotein H (open-reading frame 22) than did the 7 study subjects infected only with HHV-8. Moreover, there was a strong, inverse correlation between HIV-1 load and glycoprotein H—specific CTL lysis in the study subjects infected with both viruses. CTL reactivity to HHV-8 lytic proteins may be involved in host control of HHV-8—related diseases, such as Kaposi's sarcoma.

The possibility that an agent in addition to human immunodeficiency virus type 1 may be involved in the etiology of Kaposi's sarcoma in acquired immunodeficiency syndrome (AIDS) patients was investigated between 1984 and 1992 in this nested case-control analysis from the Multicenter AIDS Cohort Study (MACS) of homosexual and bisexual men. A total of 316 cases of Kaposi's sarcoma were identified and compared with 510 participants with AIDS and no evidence of cancer. More of the Kaposi's sarcoma cases were from Los Angeles and used a higher number of recreational drugs. The Kaposi's sarcoma cases were also more active sexually. There was a dose-response relation between Kaposi's sarcoma and the number of sexual partners, with an odds ratio of 2 between the most and least sexually active subgroups. The odds ratio for Kaposi's sarcoma increased to 4.18 (95% confidence interval 1.29–14.1) in the presence of a history of five infections. Hepatitis and gonorrhea contributed the most to this relation. The various observed odds ratios did not change after multivariate adjustment for the other risk factors. A model was developed combining all predictive associations into a composite risk score ranging from one to 12 and based on history of infections, sexual activity, use of poppers/nitrites, and having had sexual partners from the West Coast of the United States. The subgroup with the highest scores, compared to the subgroup with the lowest score, had an odds ratio of 8.93 (95% confidence interval 3.21–30.44) for Kaposi's sarcoma. A longitudinal proportional hazards analysis among all 2,190 human immunodeficiency virus type 1 -seroprevalent men at study entry, based on this risk score and CD4 cells at baseline, confirmed these findings. Identifying these specific subgroups that are at high and low risk for Kaposi's sarcoma will help future investigations to be more focused in their search for an additional etiologic factor for Kaposi's sarcoma in AIDS. Am J Epidemiol 1993; 138:256–65.

The relation between a number of potential risk factors and change in body mass index per semester was examined in a community-based cohort of 1,809 homosexual and bisexual men seropositive for human immunodeficiency virus type 1 (HIV-1). The men were followed semiannually for up to 6.5 years between 1984 and 1990. A total of 9,735 person-semesters of observations were available for analysis. A Markov-type autoregressive model, adjusting for previous body mass index, was used to predict the change in body mass index over each person-semester. Overall, the cohort was gaining weight. An asymptomatic participant 1.8 m in height whose CD4+ cell count was > 750/microliters gained a mean of 0.5 kg each person-semester. In bivariate autoregressive models, diarrhea, fever, oral thrush, acquired immunodeficiency syndrome (AIDS), and CD4+ lymphocyte counts of < 100 and 100-199 cells/microliters were all associated with a significant decrease in body mass index. A significant inverse association was also found between change in body mass index and lymphadenopathy and herpes zoster, but when the intercept coefficient was added, no overall decrease in body mass index was seen in these models. In a final multivariate model, diarrhea was less strongly associated with a change in body mass index (p = 0.057), although AIDS (p = 0.009), fever (p = 0.006), thrush (p = 0.002), and a CD4+ lymphocyte count of < 100 cells/microliters (p < 0.001) all remained independently associated with a decrease in body mass index. Lymphadenopathy and a CD4+ lymphocyte count of 100-199 cells/microliters were also significant covariates in the final model, but neither of the beta coefficients exceeded that of the intercept, indicating that they were not independently associated with a decrease in body mass index. These findings suggest that the importance of diarrhea as a cause of HIV-related weight loss may have been over-estimated in previous clinic-based studies. AIDS and nonspecific markers of progression (fever, thrush, and a CD4+ count of < 100 cells/microliters) were the best predictors of weight loss during a semester.

The authors studied the historical spread of human immunodeficiency virus type 1 (HIV–1) infection in homosexual/bisexual men and projected its future spread in these men using data from an AIDS-free cohort recruited during late 1984 in Baltimore, Maryland; Chicago, Illinois; Los Angeles, California; and Pittsburgh, Pennsylvania. Dates of preentry seroconversion in HIV-1 seroprevalent men were estimated using study entry values of hematologic variables influenced by HIV-1 infection. The authors used survival methods incorporating truncation to determine numbers/dates of seroconversion for men with a pre–1984 AIDS diagnosis who were selectively excluded by design from the 1984 AIDS-free cohort. Overall, the annual seroconversion hazard rose progressively from 0.4% in 1978 to 13.8% in 1983, dropped to 4.6% in 1985, and remained relatively stable at 1.1–2.2% from 1986 to 1990. By January 1990, almost 46% of men who were seronegative in 1978 had seroconverted. The authors estimated historical rates of spread by city, age, education, and ethnicity to examine the effects of these factors in the early and continuing stages of the HIV-1 epidemic. There were striking differences among cities with respect to pre-1985 seroconversion rates but not with respect to post-1985 seroconversion rates. Age, education, and ethnicity were all associated with 1978-1990 seroconversion rates. Future seroconversion among homosexual men was predicted assuming that the “stabilized” 1986–1990 hazards (stratified by age) observed here will be representative of future rates. Truncated Kaplan-Meier methods gave the probability of a seronegative 20-year-old man's remaining seronegative in subsequent years. Such a man has a 20.2% chance of serocon-verting before reaching the age of 25 years (a 4.4% yearly hazard). The annual hazard drops to 2.5% between 25 and 30 years, to about 1.5% between 30 and 45 years, and to 1.0% between 45 and 55 years. The overall probability of seroconversion prior to age 55 years is about 50%, with seroconversion still continuing at and after age 55. Given that this cohort consists of volunteers receiving extensive anti-HIV-1 transmission education, the futureseroconversion rates of the general homosexual population may be even higher than those observed here. Am J Epidemiol 1991 ;134:1190-1205.

Prevalence estimates of cognitive impairment in HIV disease vary widely. Here we used multivariate normative comparison (MNC) with identify individuals with impaired cognition, and to compare the results with those using the Frascati and Gisslén criteria.The current project used data collected before October 2014 from bisexual/gay men from the Multicenter AIDS Cohort Study. A total of 2904 men (mean age 39.7 years, 52.7% seropositive) had complete data in six cognitive domains at their first neuropsychological evaluation. T-scores were computed for each domain and the MNC was applied to detect impairment among seronegative and seropositive groups.The MNC classified 6.26% of seronegative men as being impaired using a predetermined 5% false discovery rate. By contrast, the Frascati and the Gisslén criteria identified 24.54 and 11.36% of seronegative men as impaired. For seropositive men, the percentage impairment was 7.45, 25.73, and 11.69%, respectively, by the MNC, Frascati and Gisslén criteria. When we used seronegative men without medical comorbidities as the control group, the MNC, the Frascati and the Gisslén criteria identified 5.05, 27.07, and 4.21% of the seronegative men, and 4.34, 30.95, and 4.48% of the seropositive men as having cognitive impairment. For each method, serostatus was not associated with cognitive impairment.The MNC controls the false discovery rate and therefore avoids the low specificity that characterizes the Frascati and Gisslén criteria. More research is needed to evaluate the sensitivity of the MNC method in a seropositive population that may be sicker and older than the current study sample and that includes women.

The present study examines sociodemographic characteristics, levels of psychological distress, and coping styles among HIV-seropositive (HIV+) gay men who either did or did not engage in sexual activity which placed others at risk for HIV infection. Risky sexual behavior was defined as engaging in insertive anal intercourse. Respondents were 156 HIV+ men enrolled at the Pittsburgh site of the Multicenter AIDS Cohort Study in 1989-90. HIV+ men who engaged in risky sexual behavior, while similar to remaining HIV+ men on most sociodemographic characteristics, showed lower levels of psychological distress and somewhat higher feelings of control over their lives. Risky men were less likely to employ active, behavioral strategies for day-to-day coping with the issues of HIV infection and AIDS, and were more likely to report using recreational drugs to reduce tension associated with thoughts about HIV. This profile of psychosocial characteristics associated with risky sexual activity may lead to further refinement of educational and other intervention strategies with HIV+ men. Implications for such strategies are discussed.

To estimate expected survival time among homosexual men infected with the human immunodeficiency virus type 1 (HIV-1) by (1) the calendar period before (1985-1988) and after (1989-1993) the widespread availability of acquired immunodeficiency syndrome (AIDS) treatments with antiretroviral and prophylactic interventions, and (2) stage of HIV disease.A prospective cohort study. A group of HIV-1-infected homosexual men were followed from July 1985 through June 1993 and evaluated every 6 months for the presence of clinical symptoms and measurement of the CD4 cell count. To measure the effectiveness of AIDS therapies in this nonrandomized study, we used 2 calendar periods as proxy measures of relative intensity of exposure to antiretroviral therapy. Stage of infection was defined by CD4 cell count and presence of HIV-related clinical symptoms or AIDS.Homosexual men infected with HIV-1 from the Multicenter AIDS Cohort Study.Survival time based on stage of HIV infection.The percentage of HIV-1-infected individuals free of AIDS and clinical symptoms at baseline who survived 2.5 years according to baseline CD4 cell counts of 0 to 0.100, 0.101 to 0.200, and 0.201 to 0.350 x 10(9)/L was 22%, 53%, and 83%, respectively, for the 1985-1988 calendar period, compared with 54%, 71%, and 91%, respectively, for men in the 1989-1993 calendar period. Among men free of AIDS with CD4 cell counts of greater than 0.350 x 10(9)/L, the relative hazard of mortality was 1.6 to 2.3 times higher for those with clinical symptoms compared with those free of clinical symptoms.Survival of AIDS-free HIV-1-infected individuals with CD4 cell counts of less than 0.350 x 10(9)/L has improved since antiretroviral and HIV prophylactic treatments have become available, but the long-term prognosis remains poor.

Reactivation of Epstein-Barr virus (EBV) in early human immunodeficiency virus (HIV) infection was investigated in 49 homosexual men who seroconverted to HIV (cases) as compared with 49 matched controls who remained seronegative to HIV during a longitudinal study. EBV infection was reactivated in cases 6 months, but not 12 months, prior to HIV seroconversion as compared with controls and remained reactivated during 18 months of follow-up after HIV seroconversion, as shown by increases in immunoglobulin (Ig) G antibody titers to EBV early antigen. Antibody titers to EBV viral capsid antigen did not differ between cases and controls prior to the time of seroconversion to HIV but were significantly increased among cases by the first seropositive study visit and remained elevated during the 18 months after HIV seroconversion. Total serum IgG levels were increased in cases at the visit of seroconversion, and during 18 months of follow-up, but did not correlate with enhanced IgG production specific for EBV antigens. Significant decreases in numbers of CD4+ cells and increases in numbers of CD8+ cells during this early phase of HIV infection were not associated with changes in patterns of EBV antibody responses. Reactivation of EBV beginning 6 months before HIV seroconversion may have implications regarding the role of this herpesvirus in the pathogenesis of HIV.

HIV infection is associated with increased prevalence of subclinical coronary plaque. The extent to which such plaque reflects effects of HIV infection or effects of long-term antiretroviral therapy (ART) use remains unclear and was the goal of this analysis.We compared the prevalence and extent of coronary plaque and stenosis between users of specific ART drugs or drug classes using coronary computed tomography (CT) among HIV-infected men in the Multicenter AIDS Cohort Study. To account for time-dependent confounders, including cardiovascular disease risk factors and time-varying reasons for using specific treatments, we conducted fully adjusted logistic and linear models with inverse probability of treatment weighting.There were 618 men who underwent noncontrast coronary CT; 450 also underwent coronary CT angiography. At the time of scanning, 81% had undetectable plasma HIV RNA. In fully adjusted models, cumulative use of zidovudine, abacavir, darunavir, and protease inhibitors as a drug class were inconsistently associated with specific forms of plaque presence or extent.Among virally suppressed HIV-infected men with extensive ART exposure, no consistent associations between use of specific ART drugs and both subclinical coronary plaque presence and extent were apparent. Our findings support the hypothesis that, among virally suppressed persons, type of ART used is not in general a major determinant of subclinical coronary plaque risk.

Background: HIV is an independent risk factor for chronic obstructive pulmonary disease; however, baseline risk factors for lung function decline remain largely unknown in this population. Methods: HIV-infected participants in the Pittsburgh Lung HIV Cohort with at least 3 pulmonary function measurements between 2007 and 2016 were included. Pulmonary function testing including postbronchodilator (BD) spirometry and diffusion capacity for carbon monoxide (DLco) was performed every 18 months. We used a mixed-effect linear model to evaluate factors associated with pulmonary function testing and DLco decline and logistic regression models to evaluate factors associated with rapid FEV1 decline (defined as &gt;80 mL per year) and any DLco decline. Results: Two hundred eighty-five HIV-infected participants were included. Median baseline CD4 cell count was 521 cells per micro liter, 61.9% had an undetectable HIV viral load at baseline, and 78.5% were receiving ART. Approximately 20% of participants met Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for a diagnosis of chronic obstructive pulmonary disease at baseline. Older age and baseline GOLD stage 1 compared with stage 0 were associated with faster decline in post-BD FEV1%, whereas female sex was associated with slower decline. Similarly, female sex was associated with slower decline in DLco%. HIV-related factors including CD4 cell count, viral load, and ART use were not significantly associated with pulmonary function decline. Conclusions: Older age, male sex, and higher baseline GOLD stage were associated with more rapid post-BD FEV1% decline in HIV-infected individuals.

Data were collected from 1614 homosexual and bisexual men in 1984 through 1985 and from 1988 to 1992 in Pittsburgh. Of the men entering the study since 1988, 16% reported engaging in unprotected anal receptive intercourse with more than one partner during the 6 months before their visit. Approximately 7% of the younger men and 18% of the men over 22 years of age in the recent cohort were already infected with the human immunodeficiency virus, the same rates as those described 8 years ago. Aggressive risk-reduction programs are needed in high schools and existing networks in the gay community.

A multiplex PCR-based assay was developed for the detection of Bordetella pertussis in nasopharyngeal swab specimens. The assay simultaneously amplified two separate DNA targets (153 and 203 bp) within a B. pertussis repetitive element and a 438-bp target within the beta-actin gene of human DNA (PCR amplification control). PCR products were detected by a sensitive and specific liquid hybridization gel retardation assay. A total of 496 paired nasopharyngeal swab specimens were tested by both the PCR-based assay and culture. Although 30 (6%) of the specimens inhibited the amplification of the beta-actin target, in all 29 specimens studied, the inhibition disappeared on repeat testing or was easily overcome with a 1:8 dilution or less of specimen digest. Of the 495 specimen pairs yielding a final evaluable result by the PCR-based assay, 19.0% were positive by the PCR-based assay, whereas 13.9% were positive by culture (P &lt; 0.0001). After resolving the PCR-positive, culture-negative results by testing an additional aliquot from these specimens by the multiplex PCR-based assay, the PCR-based assay had a sensitivity and specificity of 98.9 and 99.7%, respectively, compared with values of 73.4 and 100%, respectively, for culture. In comparison with patients with culture-confirmed pertussis, those with PCR-positive, culture-negative results were older and more likely to have had prolonged cough, immunization with pertussis vaccine, or treatment with erythromycin. This multiplex PCR-based assay is substantially more sensitive than culture and identifies specimens that contain inhibitors of PCR.

Researchers commonly express scepticism about using observational data to estimate the effect of a treatment on an outcome the treatment is intended to affect. In this paper, we consider using data from the Multicenter AIDS Cohort Study (MACS) to determine whether zidovudine prevents the development of Kaposi's sarcoma among HIV-positive gay men. Several methodologic issues common to observational data characterized the study: information on potentially important confounders was missing at some study visits; investigators did not always know the time of changes in treatment level, nor the value of confounders at that time, and the censoring process depended strongly on time-varying covariates related to outcome. We describe application to our data of Robins' paradigm for defining, modelling and estimating the effect of a time-varying treatment and show how to modify his approach to deal with the methodologic issues we have mentioned. Further, we demonstrate that relative risk regression is less well equipped to deal with these issues. We compare our results to the findings from randomized trials, and conclude that observational studies may sometimes be useful in evaluating the effect of treatment on an intended outcome. © 1998 John Wiley & Sons, Ltd.

Human immunodeficiency virus (HIV) p24 antigenemia was assessed in a longitudinal study of 52 homosexual men who developed serum antibody to HIV. Antibody seroconversion to HIV as defined by a positive HIV enzyme immunoassay (EIA) confirmed by Western (immuno-) blot was associated with three major patterns of HIV antigenemia. In the first pattern, a transient antigenemia was noted 6 (six subjects) and 12 (one subject) months prior to detection of antibody by HIV EIA and Western blot in 7 (13.5%) of the 52 men. Use of an EIA employing a recombinant envelope protein (ENV9) was able to detect antibody in four of these seven men at the time of this early antigenemia. In the second pattern, HIV p24 antigenemia occurred in 8 (15.4%) of the 52 subjects within the first 12 months after HIV antibody seroconversion. No p24 antigen was detected in the 37 (71.1%) remaining subjects. CD4+ cell numbers were lower in antigen-positive men before and after antibody seroconversion. Development of acquired immunodeficiency syndrome (AIDS) or AIDS-related complex was strongly associated with evidence of persistent p24 antigenemia during the early, postseroconversion period. HIV p24 antigenemia may be of value in determining appropriate cohorts for drug therapy trials for subjects with early-phase HIV infection.

Mild forms of HIV-associated neurocognitive disorder (HAND) remain prevalent in the combination antiretroviral therapy (cART) era. This study's objective was to identify neuropsychological subgroups within the Multicenter AIDS Cohort Study (MACS) based on the participant-based latent structure of cognitive function and to identify factors associated with subgroups.The MACS is a four-site longitudinal study of the natural and treated history of HIV disease among gay and bisexual men.Using neuropsychological domain scores, we used a cluster variable selection algorithm to identify the optimal subset of domains with cluster information. Latent profile analysis was applied using scores from identified domains. Exploratory and posthoc analyses were conducted to identify factors associated with cluster membership and the drivers of the observed associations.Cluster variable selection identified all domains as containing cluster information except for Working Memory. A three-profile solution produced the best fit for the data. Profile 1 performed below average on all domains, Profile 2 performed average on executive functioning, motor, and speed and below average on learning and memory, Profile 3 performed at or above average across all domains. Several demographic, cognitive, and social factors were associated with profile membership; these associations were driven by differences between Profile 1 and the other profiles.There is an identifiable pattern of neuropsychological performance among MACS members determined by all domains except Working Memory. Neither HIV nor HIV-related biomarkers were related with cluster membership, consistent with other findings that cognitive performance patterns do not map directly onto HIV serostatus.

Rationale: Impaired lung function is a potent independent predictor of coronary artery disease (CAD) in individuals without human immunodeficiency virus (HIV) infection; however, the relationship between lung function and CAD in HIV remains undefined.Objectives: To examine the relationship between lung function, CAD, mortality, and circulating biomarkers in HIV.Methods: Spirometry, diffusing capacity of the lung for carbon monoxide (DL CO ), emphysema, coronary artery calcium, mortality, cause of death, and biomarkers were examined in HIV-infected and uninfected individuals enrolled in a cohort study at the University of Pittsburgh.Results were then validated in the Multicenter AIDS Cohort Study (MACS) cohort.Results: We examined data on 234 participants in the Pittsburgh cohort.The mean 6 standard deviation age was 49.5 6 10.2 years old, 82.1% were male, and 67.5% were ever smokers.Among the 177 of 234 individuals with HIV infection, lower DL CO (not forced expiratory volume in 1 second or emphysema) was independently associated with greater coronary artery calcium (odds ratio, 1.43 per 10% lower DL CO ; 95% confidence interval, 1.14-1.81).HIVinfected individuals with both reduced DL CO and coronary artery calcium had a much higher mortality than those with either low DL CO or coronary calcium alone or with neither condition.Endothelin-1, a circulating biomarker of endothelial dysfunction, was associated with both lower DL CO and greater coronary artery calcium in those with HIV infection.Results were reproducible in 144 individuals enrolled in the MACS cohort; intercellular adhesion molecule 1 was the biomarker of endothelial dysfunction assessed in the MACS cohort.Conclusions: Impaired DL CO and CAD were associated with each other and with higher mortality in individuals with HIV infection.

Background: Persons living with HIV (PLWH) are at risk of developing different phenotypes of chronic lung disease, including chronic obstructive pulmonary disease. Mechanisms underlying these phenotypes are unclear. Objective: To identify clusters of peripheral inflammatory mediators associated with pulmonary function to determine inflammatory pathways and phenotypes of chronic obstructive pulmonary disease in PLWH and HIV-uninfected individuals. Methods: Study participants were PLWH and HIV-uninfected individuals enrolled in the Pittsburgh HIV Lung Cohort. Pulmonary function tests were performed for all participants. Chest computed tomographic scans were performed in a subset of PLWH. Plasma levels of 19 inflammatory mediators were measured by Luminex or ELISA. Clusters were identified based on the expression pattern of inflammatory mediators in PLWH and HIV-uninfected individuals, and the relationships among clinical parameters were evaluated within clusters by using cluster and network analyses. Results: In PLWH, we identified a distinct cluster with higher levels of Th1, Th2, and Th17 inflammatory mediators with increased complexity of these mediators and inferred presence of pathogenic Th17 cell types. Individuals in this cluster had worse airway obstruction and more radiographic emphysema. In HIV-uninfected individuals, a cluster with high-grade systemic inflammation also had worse diffusing capacity for carbon monoxide. Conclusions: Inflammatory pathways associated with pulmonary dysfunction in PLWH suggest multifaceted immune dysregulation involved in different phenotypes of pulmonary dysfunction with a potential specific contribution of the Th17 pathway to airway obstruction in PLWH. Identification of these associations may help in development of treatments that could alter the course of the disease.

Abstract Background Persons with HIV may experience greater mobility limitations than uninfected populations. Accurate tools are needed to identify persons at greatest risk of decline. We evaluated the performance of novel muscle weakness metrics (grip, grip/body mass index [BMI], grip/weight, grip/total body fat, grip/arm lean mass) and association with slowness and falls in older persons with or at risk for HIV infection as part of the work of the Sarcopenia Definitions and Outcomes Consortium (SDOC). Methods We assessed the prevalence of sarcopenia among 398 men (200 HIV+, 198 HIV−) from the Multicenter AIDS Cohort Study and 247 women (162 HIV+, 85 HIV−) from the Women’s Interagency HIV Study using previously validated muscle weakness metrics discriminative of slowness. Sensitivity and specificity were used to compare new muscle weakness and slowness criteria to previously proposed sarcopenia definitions. Results The prevalence of muscle weakness ranged from 16% to 66% among men and 0% to 47% among women. Grip/BMI was associated with slowness among men with HIV only. Grip/BMI had low sensitivity (25%–30%) with moderate to high specificity (68%–89%) for discriminating of slowness; all proposed metrics had poor performance in the discrimination of slowness (area under the curve [AUC] &amp;lt; 0.62) or fall status (AUC &amp;lt; 0.56). The combination of muscle weakness and slowness was not significantly associated with falls (p ≥ .36), with a low sensitivity in identifying those sustaining one or more falls (sensitivity ≤ 16%). Discussion Clinical utility of new sarcopenia metrics for identification of slowness or falls in men and women with or at risk for HIV is limited, given their low sensitivity.

To identify clinical and epidemiological factors associated with failure of Pneumocystis carinii pneumonia (PCP) prophylaxis in those receiving primary and secondary prophylaxis.Longitudinal cohort study of participants infected with human immunodeficiency virus type 1 in the Multicenter AIDS Cohort Study who used PCP prophylaxis regimens after their T-helper lymphocyte counts had decreased to less than 0.200 x 10(9)/L (200/microL).Occurrence or recurrence of PCP.A total of 476 participants reported taking one or more of the following regimens: trimethoprim-sulfamethoxazole (TMP-SMX), dapsone, and/or aerosolized pentamidine--367 as primary prophylaxis and 109 as secondary prophylaxis after a previous episode of PCP. A total of 92 (20%) developed PCP despite prophylaxis. The mean failure rates per person-year of follow-up were 16.0% for those receiving primary prophylaxis and 12.1% for those receiving secondary prophylaxis (P = .19). Median times to death after initiation of primary or secondary prophylaxis were 2.0 and 1.2 years, respectively. The main predictor for failure of PCP prophylaxis was profound T-helper lymphocytopenia; 86% of failures occurred after T-helper cell counts decreased to less than 0.075 x 10(9)/L and 76% occurred after counts decreased to less than 0.050 x 10(9)/L. In multivariate time-dependent analysis, when compared with counts between 0.100 x 10(9)/L and 0.200 x 10(9)/L, the risk ratio for failure with counts less than 0.050 x 10(9)/L was 2.90 (P < .001). Once T-helper cell counts were considered, fever was the only other health status indicator that predicted subsequent PCP (ie, a time-dependent risk ratio of 2.22; P = .01). Use of TMP-SMX as the prophylaxis regimen was protective but did not eliminate failure (ie, a time-dependent risk ratio of 0.55; P = .03).These findings strongly support identifying improved methods of PCP prophylaxis once T-helper cell counts decrease to less than 0.075 x 10(9)/L or 0.100 x 10(9)/L. Given this severe degree of immunosuppression, an inherently more effective regimen against P carinii is required.

There are distinct trajectories to cognitive impairment among participants in the Multicenter AIDS Cohort Study (MACS). Here we analyzed the relationship between regional brain volumes and the individual trajectories to impairment in a subsample (n = 302) of the cohort. 302 (167 HIV-infected; mean age = 55.7 yrs.; mean education: 16.2 yrs.) of the men enrolled in the MACS MRI study contributed data to this analysis. We used voxel-based morphometry (VBM) to segment the brain images to analyze gray and white matter volume at the voxel-level. A Mixed Membership Trajectory Model had previously identified three distinct profiles, and each study participant had a membership weight for each of these three trajectories. We estimated VBM model parameters for 100 imputations, manually performed the post-hoc contrasts, and pooled the results. We examined the associations between brain volume at the voxel level and the MMTM membership weights for two profiles: one considered "unhealthy" and the other considered "Premature aging." The unhealthy profile was linked to the volume of the posterior cingulate gyrus/precuneus, the inferior frontal cortex, and the insula, whereas the premature aging profile was independently associated with the integrity of a portion of the precuneus. Trajectories to cognitive impairment are the result, in part, of atrophy in cortical regions linked to normal and pathological aging. These data suggest the possibility of predicting cognitive morbidity based on patterns of CNS atrophy.

Ambulatory function predicts morbidity and mortality and may be influenced by cardiopulmonary dysfunction. Persons living with HIV (PLWH) suffer from a high prevalence of cardiac and pulmonary comorbidities that may contribute to higher risk of ambulatory dysfunction as measured by 6-minute walk test distance (6-MWD). We investigated the effect of HIV on 6-MWD.PLWH and HIV-uninfected individuals were enrolled from 2 clinical centers and completed a 6-MWD, spirometry, diffusing capacity for carbon monoxide (DLCO) and St. George's Respiratory Questionnaire (SGRQ). Results of 6-MWD were compared between PLWH and uninfected individuals after adjusting for confounders. Multivariable linear regression analysis was used to determine predictors of 6-MWD.Mean 6-MWD in PLWH was 431 meters versus 462 in 130 HIV-uninfected individuals (p = 0.0001). Older age, lower forced expiratory volume (FEV1)% or lower forced vital capacity (FVC)%, and smoking were significant predictors of decreased 6-MWD in PLWH, but not HIV-uninfected individuals. Lower DLCO% and higher SGRQ were associated with lower 6-MWD in both groups. In a combined model, HIV status remained an independent predictor of decreased 6-MWD (Mean difference = -19.9 meters, p = 0.005).HIV infection was associated with decreased ambulatory function. Airflow limitation and impaired diffusion capacity can partially explain this effect. Subjective assessments of respiratory symptoms may identify individuals at risk for impaired physical function who may benefit from early intervention.

Abstract Background The total QT interval comprises both ventricular depolarization and repolarization currents. Understanding how HIV serostatus and other risk factors influence specific QT interval subcomponents could improve our mechanistic understanding of arrhythmias. Methods Twelve‐lead electrocardiograms (ECGs) were acquired in 774 HIV‐infected (HIV+) and 652 HIV‐uninfected (HIV−) men from the Multicenter AIDS Cohort Study. Individual QT subcomponent intervals were analyzed: R‐onset to R‐peak, R‐peak to R‐end, JT segment, T‐onset to T‐peak, and T‐peak to T‐end. Using multivariable linear regressions, we investigated associations between HIV serostatus and covariates, including serum concentrations of inflammatory biomarkers such as interleukin‐6 (IL‐6), and each QT subcomponent. Results After adjustment for demographics and risk factors, HIV+ versus HIV− men differed only in repolarization phase durations with longer T‐onset to T‐peak by 2.3 ms (95% CI 0–4.5, p &lt; .05) and T‐peak to T‐end by 1.6 ms (95% CI 0.3–2.9, p &lt; .05). Adjusting for inflammation attenuated the strength and significance of the relationship between HIV serostatus and repolarization. The highest tertile of IL‐6 was associated with a 7.3 ms (95% CI 3.2–11.5, p &lt; .01) longer T‐onset to T‐peak. Age, race, body mass index, alcohol use, and left ventricular hypertrophy were each associated with up to 2.2–12.5 ms longer T‐wave subcomponents. Conclusions HIV seropositivity, in combination with additional risk factors including increased systemic inflammation, is associated with longer T‐wave subcomponents. These findings could suggest mechanisms by which the ventricular repolarization phase is lengthened and thereby contribute to increased arrhythmic risk in men living with HIV.

Objectives Elite controllers (ECs), viraemic controllers (VCs), and long‐term nonprogressors (LTNPs) control HIV viral replication or maintain CD4 T‐cell counts without antiretroviral therapy, but may have increased cardiovascular disease (CVD) risk compared to HIV‐uninfected persons. We evaluated subclinical carotid and coronary atherosclerosis and inflammatory biomarker levels among HIV controllers, LTNPs and noncontrollers and HIV‐uninfected individuals in the Multicenter AIDS Cohort Study (MACS) and the Women’s Interagency HIV Study (WIHS). Methods We measured carotid plaque presence and common carotid artery intima‐media thickness (IMT) in 1729 women and 1308 men, and the presence of coronary artery calcium and plaque in a subgroup of men. Associations between HIV control category and carotid and coronary plaque prevalences were assessed by multivariable regression analyses adjusting for demographics and CVD risk factors. Serum inflammatory biomarker concentrations [soluble CD163 (sCD163), soluble CD14 (sCD14), galectin‐3 (Gal‐3), galectin‐3 binding protein (Gal‐3BP) and interleukin (IL)‐6] were measured and associations with HIV control category assessed. Results We included 135 HIV controllers (30 ECs) and 135 LTNPs in the study. Carotid plaque prevalence and carotid IMT were similar in HIV controllers, LTNPs and HIV‐uninfected individuals. HIV controllers and LTNPs had lower prevalences of carotid plaque compared to viraemic HIV‐infected individuals. The prevalence of coronary atherosclerosis was similar in HIV controllers/LTNPs compared to HIV‐uninfected and viraemic HIV‐infected men. Controllers and LTNPs had higher concentrations of sCD163 and sCD14 compared to HIV‐uninfected persons. Conclusions Subclinical CVD was similar in HIV controllers, LTNPs and HIV‐uninfected individuals despite elevated levels of some inflammatory biomarkers. Future studies of HIV controllers and LTNPs are needed to characterize the risk of CVD among HIV‐infected persons.

Objective: To determine whether combination antiretroviral therapy (cART) initiation alters the trajectory of cognitive performance in HIV+ men, and whether cognition prior to cART predicts postcART function. Design: Longitudinal cohort study. Multicenter AIDS Cohort Study. Methods: From an initial set of 3701 men with complete neuropsychological data, men with HIV infection were initially matched with men without infection on cognitive status, race, age, and timeline (T 0 defined as cART initiation). Propensity score matching was then used to match pairs on depressive symptoms at T 0 , education, T 0 cognitive scores, and recruitment cohort. There were 506 matched pairs of infected and uninfected men in the final analysis. Mixed effect models were constructed to analyze the trajectories of cognitive functions and to test the effect of cART and HIV on cognitive functions over time. Results: Performance in each cognitive domain did not change following the initiation of cART among HIV-infected men with prior impairment and was comparable to the performance of their matched uninfected men. However, among the infected men who were unimpaired prior to cART, motor function declined significantly faster than it did for uninfected controls. Conclusions: Cognitive dysfunction is persistent in HIV-infected men and cART does not alter the trajectory of cognitive decline in men who were impaired prior to effective therapy. This suggests that current cognitive impairment in HIV+ men results from a legacy effect, and from factors other than the HIV itself. Furthermore, motor skills may be uniquely vulnerable to the virus, cART, or age-related co-morbidities.

A novel internally controlled PCR (ICPCR) assay was developed to accurately quantitate human immunodeficiency virus type 1 (HIV-1) DNA and RNA in peripheral blood mononuclear cells and plasma. The ICPCR assay was sensitive and reproducible within a linear range of amplification of 10(0) to 10(3) copies for HIV-1 DNA and 10(1) to 10(4) copies for HIV-1 RNA. The assay detected HIV-1 RNA in plasma and peripheral blood mononuclear cells from all HIV-1 subjects regardless of disease stage. ICPCR was compared with a branched-DNA signal amplification assay for subjects beginning antiretroviral therapy. The reductions in plasma HIV-1 RNA in response to therapy were comparable with the two assays. The ICPCR assay should be useful in monitoring HIV-1 RNA levels both in natural history studies and in clinical trials of antiretroviral agents.

Site-specific shedding of cytomegalovirus (CMV) was assessed in a longitudinal study of homosexual and bisexual men. At initial testing, CMV was cultured from the semen of 33% (19 of 58) of asymptomatic and mildly symptomatic men who were seropositive for human immunodeficiency virus (HIV) at the time of entry into the study, whereas it was cultured from the semen of 17% (10 of 58) of the men who were HIV seronegative. CMV was isolated much more frequently from semen than from urine or throat washing specimens, and it was rarely recovered from stool or blood, regardless of the subject's HIV serostatus. CMV was cultured from the semen of 31% (16 of 52) of the men relatively early after seroconversion to HIV (mean, 12.8 months). CMV was persistently isolated from the semen of a greater proportion of the HIV-seropositive men than from the semen of the HIV-seronegative men during a 4.5-year follow-up period (52 of 110 - [47%] and 15 of 58 [26%] men, respectively). There was an increased relative risk for shedding of CMV in semen in association with decreased CD4+ cell numbers and increased levels of serum immunoglobulin A. However, there was no association of CMV shedding with an increased risk for the development of AIDS.

Abstract Sexual practices continue to be the major mode of Human Immunodeficiency Virus (HIV) transmission within the homosexual population. Failure to use condoms consistently during anal intercourse has been directly associated with use of alcohol and other substances. We identify psychosocial cofactors that are not only related to sexual practices, but are also associated with an increased likelihood that substance users will engage in high-risk sex. Subjects were 525 men enrolled at the Pittsburgh site of the Multicenter AIDS Cohort Study in 1989. Alcohol use and popper use were each significantly associated with high-risk sexual practices (i.e., unprotected anal intercourse with multiple partners), even after a broad array of psychosocial characteristics were controlled. In addition, younger men, and those with greater family support and a higher sense of mastery, were more likely to engage in risky behavior. Not only did such “main effects” emerge, but the substance use-sexual practice relationship was particularly strong in certain sub-cohorts of the sample. Thus, frequent popper users were more likely to engage in high-risk behavior if they were younger; had less depressive symptomatology; or had a poorer sense of mastery. Identification of subcohorts may foster the development of more carefully targeted education intervention efforts.

Studies demonstrate that Tropheryma whipplei (T. whipplei) is present in the lungs of healthy individuals without acute respiratory symptoms or acute respiratory infection and is more common in the lungs of HIV-infected individuals and in smokers. The impact of T. whipplei colonization in the lung on local inflammation and pulmonary dysfunction in HIV-infected individuals is currently unknown. In this study, we performed specific polymerase chain reaction (PCR) and sequencing for T. whipplei in bronchoalveolar lavage (BAL) and induced sputum (IS) samples in 76 HIV-infected participants from three clinical sites. Pulmonary function and proinflammatory cytokine and chemokine levels in BAL were measured. Frequency of T. whipplei in either BAL or IS was 43.4%. The sensitivity and specificity of IS compared to BAL for detection of T. whipplei was 92.3% and 84.2%, respectively, and isolates of T. whipplei in the BAL and IS in the same subject shared genetic identity. Pulmonary function measures were not associated with T. whipplei colonization, and proinflammatory cytokine and chemokine levels in BAL and plasma as well as percentages of inflammatory cells in BAL and IS were not higher in colonized individuals. Overall, these results indicate that T. whipplei colonization in the lung is common, but may not be associated with decreased pulmonary function or inflammation in HIV-infected individuals.

In the general population, metabolic health often declines as BMI increases. However, some obese individuals maintain metabolic health. HIV and antiretroviral therapy have been associated with metabolic disturbances. We hypothesized that HIV-infected (HIV) men on suppressive antiretroviral therapy experience less metabolic health than HIV-uninfected (HIV) men across all BMI categories.In a cross-sectional analysis of 1018 HIV and 1092 HIV men enrolled in the multicenter AIDS cohort study, Poisson regression with robust variance determined associations between HIV serostatus and metabolic health prevalence (defined as meeting ≤2 of 5 National Cholesterol Education Program Adult Treatment Panel III metabolic syndrome criteria), adjusting for age, race, BMI category, smoking, and hepatitis C virus infection status.HIV men were younger (54 vs. 59 years) and had lower median BMI (25 vs. 27 kg/m). Nonobese HIV men had lower metabolic health prevalence than HIV men (BMI ≤25 kg/m: 80 vs. 94%, P < 0.001; BMI 25-29 kg/m: 64 vs. 71%, P = 0.05), but metabolic health prevalence among obese men did not differ by HIV serostatus (BMI 30-34 kg/m: 35 vs. 39%, P = 0.48; BMI ≥35 kg/m: 27 vs. 25%, P = 0.79). In the adjusted model, nonobese HIV men were less likely to demonstrate metabolic health than nonobese HIV men. Among HIV men, per year darunavir, zidovudine, and stavudine use were associated with lower metabolic health likelihood.Metabolically healthy obesity prevalence does not differ by HIV serostatus. However, among nonobese men, HIV infection is associated with lower metabolic health prevalence, with associations between lack of metabolic health and darunavir and thymidine analog nucleoside reverse transcriptase inhibitor exposure observed.

HIV-infected men have increased rates of osteoporosis and fracture compared to HIV-uninfected men. Testosterone use among HIV-infected men is common. In HIV-uninfected men, testosterone increases bone mineral density (BMD), but its effects have not been evaluated in HIV-infected men. In a substudy of Multicenter AIDS Cohort Study (MACS), the Bone Strength Substudy (BOSS) enrolled 202 HIV-infected and 201 HIV-uninfected men aged between 50 and 69 years. Study participants underwent dual-energy X-ray absorptiometry (DXA) at the lumbar spine (LS), total hip (TH), and femoral neck (FN) and detailed assessment of osteoporosis risk factors. We used multivariable linear regression to determine associations and 95% confidence intervals (CIs) between self-reported testosterone use and T-scores at the LS, TH, and FN after adjustment for demographics, behavioral covariates, comorbidities, and other traditional osteoporosis risk factors. HIV-infected men reported more frequent testosterone use (22% vs. 4%; p < .001) and had lower median BMD T-score at TH than HIV-uninfected men (0.0 vs. 0.3; p = .045) but similar T-scores at LS and FN. In the overall study population, testosterone use was associated with significantly greater BMD T-score at LS (0.68; 95% CI: 0.22-1.13). In HIV-infected men with virologic suppression, testosterone was significantly associated with higher BMD T-score at LS (0.95; 95% CI: 0.36-1.54) and TH (0.45; 95% CI: 0.04-0.86). Current testosterone use is common in HIV-infected men and was associated with higher BMD, compared to those not taking testosterone. Testosterone's role in reducing fracture risk in HIV-infected men should be investigated.

Clostridium difficile infection (CDI) is a leading cause of hospital-associated infections. Antibiotic stewardship, environmental disinfection, and reduction of transmission via health care workers are the major modes of CDI prevention within hospitals.The aim of this study was to evaluate the role of the environment in the spread of CDI within hospital rooms. Bed tracing of positive-CDI inpatients was performed to detect the strength of association to specific rooms. Environmental cultures were conducted to identify adequacy of environmental C difficile (CD) spores. Whole-genome sequencing was performed to evaluate the degree of CD relatedness.Bed tracing performed for 211 CDI patients showed a limited list of high-burden rooms. Environmental cultures for surfaces disinfected with a sporicidal agent were almost entirely negative, whereas the floors were positive for CDI in 15% of the studied patient rooms. Whole-genome sequencing did not detect any close genetic relatedness.Unlike in an outbreak setting, bed tracing did not yield conclusive results of room reservoirs. The C diff Banana Broth culture was inexpensive, sensitive, and easy to incubate under aerobic conditions. Sporicidal disinfectants were effective in eliminating CD from the environment. CD spores were found on floors and hard-to-clean surfaces.

Objectives Adipose tissue (AT) density measurement may provide information about AT quality among people living with HIV. We assessed AT density and evaluated relationships between AT density and immunometabolic biomarker concentrations in men with HIV. Design Cross-sectional analysis of men enrolled in the Multicenter AIDS Cohort Study. Methods Abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) density (Hounsfield units, HU; less negative = more dense) were quantified from computed tomography (CT) scans. Multivariate linear regression models described relationships between abdominal AT density and circulating biomarker concentrations. Results HIV+ men had denser SAT (−95 vs −98 HU HIV−, P &lt; 0.001), whereas VAT density was equivalent by HIV serostatus men (382 HIV−, 462 HIV+). Historical thymidine analog nucleoside reverse transcriptase inhibitor (tNRTI) use was associated with denser SAT but not VAT. In adjusted models, a 1 s.d. greater SAT or VAT density was associated with higher levels of adiponectin, leptin, HOMA-IR and triglyceride:HDL cholesterol ratio and lower hs-CRP concentrations in HIV− men. Conversely, in HIV+ men, each s.d. greater SAT density was not associated with metabolic parameter improvements and was significantly ( P &lt; 0.05) associated with higher systemic inflammation. Trends toward higher inflammatory biomarker concentrations per 1 s.d. greater VAT density were also observed among HIV+ men. Conclusions Among men living with HIV, greater SAT density was associated with greater systemic inflammation independent of SAT area. AT density measurement provides additional insight into AT density beyond measurement of AT quantity alone, and may have implications for metabolic disease risk.

The rate at which immunodeficiency develops in untreated human immunodeficiency virus type 1(HIV-1)-infected persons might be increasing or decreasing over time because of viral evolution or other factors. Beginning in 1984, Multicenter AIDS Cohort Study investigators recruited HIV-1-seronegative homosexual/bisexual men from four US metropolitan areas and examined them semiannually for HIV-1 seroconversion. To assess possible secular changes in the natural history of HIV-1 infection, the authors examined CD4+ lymphocyte data from 354 men who seroconverted between 1984 and 1991. To control for measurement differences among centers and over time, the authors adjusted CD4+ lymphocyte values to those of persistently seronegative participants. CD4+ lymphocyte percentage measurements at the first seropositive visit formed a U-shaped pattern, with the lowest values observed in 1988 and 1989. The authors observed no consistent secular pattern of CD4+ percentages at later visit dates, except that mean CD4+ percentages were consistently lowest in men who seroconverted in 1988. In a proportional hazards model, the time to the adjusted CD4+ lymphocyte count of < 500 cells/mm3 was not associated with the secular time of seroconversion (relative hazard = 1.05, 95% confidence interval 0.97-1.13). The authors' data do not suggest a major change in the natural history of HIV-1 infection of this population.

Four hundred sixty-four homosexual and bisexual men, recruited from a cohort of 1,700 men enrolled in a study of the natural history of acquired immunodeficiency syndrome (AIDS), participated in a peer-led, small-group educational session promoting AIDS risk reduction. Although levels of knowledge about AIDS and human Immunodeficiency virus (HIV) transmission were uniformly high prior to intervention, at least 60% of the men reported having engaged in unprotected, receptive anal intercourse with more than one partner in the preceding six months. Prior to intervention, a substantial number of the men had mixed feelings about AIDS risk reduction or endorsed negative attitudes about AIDS risk reduction. After attending the session, attitudes improved significantly in five of the six areas surveyed. The ability of a group educational session to influence attitudes about AIDS risk reduction in a positive way suggests that this type of intervention may be effective in enabling homosexual and bisexual men to adopt low-risk sexual activities by influencing the nonhealth motives of sexual behavior, especially peer norms about safe sex. Long-term follow-up of this cohort will test for maintenance of this attitudinal change and, more importantly, will evaluate whether this attitudinal change is predictive of future changes in sexual behavior and HIV seroconversion rates. The authors stress the importance of incorporating existing health promotion research findings into the design and evaluation of AIDS risk reduction programs.

Abnormalities in the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) axis have been observed in HIV-infected persons and have been implicated in cardiovascular disease (CVD) pathogenesis in the general population.To determine associations of serum OPG and RANKL concentrations with HIV infection and subclinical atherosclerosis.Cross-sectional study nested within the Multicenter AIDS Cohort Study.Four US academic medical centers.There were 578 HIV-infected and 344 HIV-uninfected men.Coronary artery calcium (CAC) was measured by noncontrast cardiac computed tomography, and coronary stenosis and plaque characteristics (composition, presence, and extent) were measured by coronary computed tomography angiography. All statistical models were adjusted for traditional CVD risk factors.OPG concentrations were higher, and RANKL concentrations were lower among HIV-infected men compared with HIV-uninfected men (P < 0.0001 each). Among HIV-infected men, higher OPG concentrations were associated with the presence of CAC, mixed plaque, and coronary stenosis >50%, but not with plaque extent. In contrast, among HIV-uninfected men, higher OPG concentrations were associated with the extent of both CAC and calcified plaque, but not with their presence. RANKL concentrations were not associated with plaque presence or the extent among HIV-infected men, but among HIV-uninfected men, lower RANKL concentrations were associated with greater extent of CAC and total plaque.OPG and RANKL are dysregulated in HIV-infected men, and their relationship to the presence and extent of subclinical atherosclerosis varies by HIV status. The role of these biomarkers in CVD pathogenesis and risk prediction may be different in HIV-infected men.

The purpose of this study is to determine if a new score calculated with coronary artery calcium (CAC) density and volume is associated with total coronary artery plaque burden and composition on coronary CT angiography (CCTA) compared to the Agatston score (AS).We identified 347 men enrolled in the Multicenter AIDS cohort study who underwent contrast and non-contrast CCTs, and had CAC>0. CAC densities (mean Hounsfield Units [HU]) per plaque) and volumes on non-contrast CCT were measured. A Density-Volume Calcium score was calculated by multiplying the plaque volume by a factor based on the mean HU of the plaque (4, 3, 2 and 1 for 130-199, 200-299, 300-399, and ≥400HU). Total Density-Volume Calcium score was determined by the sum of these individual scores. The semi-quantitative partially calcified and total plaque scores (PCPS and TPS) on CCTA were calculated. The associations between Density-Volume Calcium score, PCPS and TPS were examined.Overall, 2879 CAC plaques were assessed. Multivariable linear regression models demonstrated a stronger association between the log Density-Volume Calcium score and both the PCPS (β 0.99, 95%CI 0.80-1.19) and TPS (β 2.15, 95%CI 1.88-2.42) compared to the log of AS (PCPS: β 0.77, 95%CI 0.61-0.94; TPS: β 1.70, 95%CI 1.48-1.94). Similar results were observed for numbers of PC or TP segments.The new CAC score weighted towards lower density demonstrated improved correlation with semi-quantitative PC and TP burden on CCTA compared to the traditional AS, which suggests it has utility as an alternative measure of atherosclerotic burden.

We aimed to determine the relationship of circulating adipokines and inflammatory biomarkers with fatty liver among men in the Multicenter AIDS Cohort Study.Noncontrast computed tomography was used to assess fatty liver and measure abdominal visceral adipose tissue (VAT) area in 526 participants without history of cardiovascular disease, heavy alcohol use, or viral hepatitis infection. Multivariable logistic regression was used to assess associations of circulating biomarker levels with fatty liver.Three hundred twenty-nine human immunodeficiency virus (HIV)-infected men had higher levels of several inflammatory biomarkers compared with 197 HIV-uninfected men. Among HIV-uninfected men, increased adiponectin was associated with lower odds of fatty liver (odds ratio [OR] = 0.51 per doubling, P = .02), whereas higher odds of fatty liver was observed with increased levels of the proinflammatory markers intercellular adhesion molecule (ICAM)-1 (OR = 5.30, P = .004), C-reactive protein (OR = 1.66, P = .002), interleukin (IL)-6 (OR = 1.67, P = .03), and tumor necrosis factor α receptor 2 (OR = 6.55, P = .003). Among HIV-infected men, ICAM-1 was the only proinflammatory marker associated with greater odds of fatty liver (OR = 2.67, P = .02), whereas higher adiponectin (OR = 0.57, P = .003), and osteoprotegerin levels (OR = 0.48, P = .03) were associated with lower odds. These associations were all independent of VAT.Fatty liver is associated with a heightened inflammatory state independent of visceral adiposity in HIV-uninfected men but not in HIV-infected men. However, a heightened anti-inflammatory state may protect against fatty liver regardless of HIV serostatus.

Factors affecting kidney function and proteinuria among HIV-positive (HIV+) and HIV-negative (HIV-) persons need better characterization.We evaluated estimated glomerular filtration rate (eGFR, ml/min per 1.73 m) changes, proteinuria prevalence (a urine protein-to-creatinine ratio of ≥0.2 at two consecutive visits) and associated factors among HIV+ and HIV- men.There were 917 HIV+ men receiving HAART, 159 HIV+ men not receiving HAART, and 1305 HIV- men seen from October 2003 to September 2014. Median annual eGFR change was -0.5, -0.8% for HIV+ and -0.3% for HIV- men (P < 0.001). Factors significantly (P < 0.05) associated with more than 3% annual eGFR decline were HAART receipt (but no specific antiretroviral drug), age more than 50, hypertension, diabetes, current smoking. Proteinuria existed in 14.9% of visit-pairs among HAART recipients, 5.8% among non-HAART recipients, and 1.9% among HIV- men, and was associated with subsequent annual more than 3% eGFR decline (odds ratio 1.80, P < 0.001). Proteinuria-associated factors also included HAART use (vs. HIV-), age at least 50 (vs. <40), diabetes, hypertension, current smoking, hepatitis C virus-infection (all P < 0.05) and, among HIV+ men, lower CD4 cell count, didanosine, saquinavir, or nelfinavir use (all P < 0.05). After adjusting for proteinuria, among HAART users, having a detectable HIV RNA, cumulative use of tenofovir disoproxil fumarate, emtricitabine, ritonavir, atazanavir, any protease inhibitor, or fluconazole were associated with more than 3% annual eGFR decline.Longitudinal kidney function decline was associated with HAART use but no individual antiretroviral drug, and traditional kidney disease risks. Proteinuria was nearly seven times more common in HAART-treated men than HIV- men, reflected recent eGFR decline and predicted subsequent eGFR decline.

Background: Diabetes mellitus is a major comorbidity in people with HIV (PWH). Hyperglycemia below diabetic range defines prediabetes (prediabetes mellitus). We compared the progression from prediabetes mellitus to diabetes mellitus in PWH and people without HIV (PWOH). Methods: Fasting glucose was measured semiannually in the MACS since 1999. Men with prediabetes mellitus (fasting glucose between 100 and 125 mg/dl, confirmed within a year by fasting glucose in the prediabetes mellitus range or HbA1c between 5.7 and 6.4%) were included. The first visit with prediabetes mellitus was the baseline visit. Incident diabetes mellitus was defined as fasting glucose at least 126 mg/dl, confirmed at a subsequent visit, or self-reported diabetes mellitus, or use of anti-diabetes mellitus medication. We used binomial transition models to compare the progression from prediabetes mellitus to diabetes mellitus by HIV serostatus, adjusted for age, number of previous prediabetes mellitus to diabetes mellitus transitions, ethnicity, BMI, family history of diabetes mellitus, and hepatitis C virus (HCV) infection. Results: Between 1999 and 2019, 1584 men (793 PWH; 791 PWOH) with prediabetes mellitus were included. At baseline, PWH were younger (48 vs. 51 years, P &lt; 0.01), had lower BMI (26 vs. 27), were more frequently nonwhite (47 vs. 30%), and HCV-infected as per last measure (8 vs. 4%) than PWOH (all P &lt; 0.01). Over a median 12-year follow-up, 23% of participants developed diabetes mellitus. In adjusted analyses, the risk for incident diabetes mellitus was 40% (95% CI: 0--80%) higher among PWH than PWOH ( P = 0.04). Conclusion: Among men with prediabetes mellitus, PWH had an increased risk of incident diabetes mellitus adjusted for competing risk factors, warranting the evaluation of diabetes mellitus prevention strategies.

Background: Sex hormone–binding globulin (SHBG) is a glycoprotein that regulates sex hormone bioavailability and increases with age in the general population. SHBG concentrations are higher in people with HIV, a population in whom accelerated aging has been hypothesized. It is unclear whether longitudinal changes in SHBG increase over time and differ by HIV serostatus. Methods: In a longitudinal study, SHBG was measured in 182 men with HIV (MWH) and 267 men without HIV (seronegative) from the Multicenter AIDS Cohort Study and matched for age, race, site, and time, with ≥2 SHBG serum samples over the 10 years after HAART initiation. Multivariable linear mixed-effects regression models were used to evaluate whether log-transformed SHBG [ln(SHBG)] and its rate of change differed by HIV serostatus. Results: At baseline, the mean age in MWH was similar to that in HIV-seronegative men (51 ± 5 vs 49 ± 6 years). However, SHBG mean values were higher in MWH compared with those in HIV-seronegative men (65.6 ± 48.8 vs. 45.4 ± 22 nmol/L, P &lt; 0.001). In a fully adjusted model, SHBG increased over time and at a faster rate in MWH compared with that in HIV-seronegative men: [2.0%/year (95% CI: 1.4 to 2.7) vs 1.3%/year (95% CI: 0.8 to 1.8), respectively, P = 0.038]. Among MWH, higher SHBG concentrations were significantly associated with lower CD4 + T-cell count [β= −0.02 (95% CI: −0.03 to −0.0002), P &lt; 0.05], fewer cumulative years on zidovudine [β = −0.027 (95% CI: −0.045 to −0.009), P &lt; 0.001], and greater cumulative years on nonnucleoside reverse transcriptase inhibitors drugs [β = 0.022 (95% CI: 0.0006 to 0.04), P &lt; 0.05]. Conclusions: Aging-related increases in SHBG were faster in MWH compared with those in HIV-seronegative men and were related to poorer immunologic status and antiretroviral medication exposure. The mechanisms and consequences of these findings require further investigation.

Recent reports have suggested that HSV-2 infection and associated anogenital ulcerations represent an important risk factor for acquisition of HIV infection. Although this is an appealing biological hypothesis, inferences drawn for homosexual men, as well as other at-risk populations, must be made after careful consideration of methods to control for potential confounding data. This report utilized a nested case-control study in which 49 homosexual HIV seroconverters were compared to 49 homosexual seronegative men matched on the prior level of receptive anal intercourse. No differences were observed for prior HSV-2 infection, since 21/49 (43%) of matched HIV seronegative men were HSV-2 antibody positive and 21/49 (43%) of HIV seroconverters were HSV-2 antibody positive at the visit 6 months before HIV seroconversion (odds ratio of 1.0, 95% confidence limits of 0.3-2.9) Similar findings were also observed for prior HSV-1 infection. Both self-reported symptoms and physical exam findings suggestive of HSV infection were rare during the 12 months prior to seroconversion and not associated with HIV seroconversion. These data do not support HSV-2 as a risk factor for seroconversion to HIV among homosexual men studied. These results should not be generalized to heterosexual transmission of HIV, particularly in Africa, where both an increased prevalence of genital ulcerative diseases and different etiologies have been observed.

A homozygous 32-bp deletion in the gene encoding CCR5, a major coreceptor for HIV-1, leads to resistance to infection with HIV-1, and heterozygosity for the deletion is associated with delayed disease progression in persons infected with HIV-1. We investigated the effect of CCR5 heterozygosity on disease progression as measured by both CD4+ T-cell count decline and the occurrence of clinical AIDS symptoms. Using a unified statistical model for CD4 count progression and AIDS development, we examined whether the effect of CCR5 heterozygosity on clinical AIDS is direct or indirect through its effect on CD4 counts. Based on data from the Multicenter AIDS Cohort Study, we noted a protective effect of CCR5 heterozygosity on both CD4 cell count progression and on AIDS occurrence. Furthermore, we found that this protective effect on the occurrence of AIDS was completely mediated through an effect on the CD4 marker. Additional adjustment for the effect of an initial viral load measurement indicate that CCR5 heterozygosity did not have predictive value for either CD4 progression or the development of AIDS beyond its association with early viral load.

Despite effective antiretroviral therapy (HAART) and durable viral suppression, many HIV-infected individuals still do not achieve CD4 cell count (CD4) normalization. Vitamin D has immunoregulatory functions, including inducing the development of T cells and higher levels may improve CD4 rebound.Longitudinal study of men from the Multicenter AIDS Cohort Study who virally suppressed following HAART initiation and had pre-HAART and post-HAART 25(OH)D and 1,25(OH)2D measurements and repeated measures of CD4.CD4 rebound was modeled using a nonlinear mixed effects model. We estimated the adjusted effect (adjusted for pre-HAART antiretroviral exposure, black race, age and CD4 at HAART initiation) of pre-HAART and post-HAART vitamin D metabolite levels on the rate of CD4 increase and final CD4 plateau.Among the 263 HIV-infected HAART initiators with pre-HAART vitamin D measurements, a 1-SD higher pre-HAART 25(OH)2D level was associated with a 9% faster rate of rise (P = 0.02) but no gain in final CD4 plateau. In contrast, a 1-SD higher 1,25(OH)2D level was associated with a 43-cell lower final CD4 (P = 0.04). Among 560 men with post-HAART measurements, findings were similar to those for pre-HAART 25(OH)2D with 1-SD higher level associated with faster rate of rise but no improvement in final CD4.We found no evidence that higher vitamin D metabolite levels pre-HAART or post-HAART are associated with better CD4 outcomes among HIV-infected HAART initiators. However, the value of pre-HAART 1,25(OH)2D levels as an indicator of immune response dysregulation could be further explored.

Objective: Whether HIV modifies the relationship of serum lipids with coronary atherosclerosis and coronary plaque subtypes is uncertain. We examined the associations between traditional lipids and coronary atherosclerosis among HIV-infected (HIV+) and HIV-uninfected (HIV−) men. Design: The Multicenter AIDS Cohort Study is an observational cohort with a total of 429 HIV+ and 303 HIV− men who had non-contrast cardiac computed tomography performed to measure coronary artery calcium and coronary computed tomography angiography to measure coronary stenosis, coronary plaque presence, and composition. Methods: We used multivariable adjusted prevalence ratios to examine the relationship between the SD difference in each lipid parameter and coronary atherosclerosis. Results: Total cholesterol (TC)/HDL-cholesterol had the strongest associations with coronary atherosclerosis regardless of HIV status. Overall, lipid parameters were most strongly associated with the presence of mixed plaque, stenosis more than 50%, and coronary artery calcium for both HIV+ and HIV− men. HIV+ men had similar, but weaker associations, between lipid parameters and coronary atherosclerosis compared with HIV− men. The strongest association was between the TC/HDL-cholesterol and stenosis more than 50% for both HIV+ [prevalence ratios 1.25 per SD (95% confidence interval 1.07–1.43)] and HIV− men [prevalence ratios 1.46 per SD (95% confidence interval 1.08–1.85)]. Conclusion: The associations between lipids and coronary atherosclerosis tended to be weaker for HIV+ compared with HIV− men, although TC/HDL had the strongest association for both HIV+ and HIV− men. A weaker association between lipid levels and coronary atherosclerosis for HIV+ men may contribute to the decreased discrimination of cardiovascular disease risk observed in HIV+ individuals.

Increasing body mass index (BMI) is generally associated with loss of metabolic health, although some obese individuals remain metabolically healthy. Among nonobese men, HIV infection has been associated with a lower prevalence of metabolic health.We conducted a cross-sectional analysis of 470 HIV-infected and 368 HIV-uninfected men enrolled in the Multicenter AIDS Cohort Study Cardiovascular substudy. Circulating biomarker levels were compared by BMI category and by HIV serostatus. Poisson regression with robust variance determined associations between metabolic health and circulating inflammatory biomarker levels after adjusting for factors previously associated with metabolic health.HIV-infected men were younger and less likely to be obese. Among HIV-infected, normal weight metabolically healthy men (compared to unhealthy) had significantly lower circulating levels of interleukin- (IL-) 6, soluble tumor necrosis factor receptors (sTNFR) I and II, and homeostatic model assessment of insulin resistance (HOMA-IR), higher adiponectin, less visceral fat, and more subcutaneous fat. Among HIV-uninfected normal weight men and obese men (regardless of HIV serostatus), metabolic health was associated only with higher levels of adiponectin, less visceral fat, and lower HOMA-IR values. In multivariate analyses restricted to HIV-infected men, lower hs-CRP, sTNFRI, sTNFRII, and HOMA-IR and higher adiponectin levels were associated with metabolic health. Additional adjustment for visceral adiposity did not alter results.Among HIV-infected normal weight men, metabolic health was associated with less systemic inflammation, a relationship that, among normal weight men, was unique to HIV+ men and did not exist among obese men of either HIV serostatus.

Despite much investigation of zidovudine, little has been reported regarding its effect on the development of most individual AIDS-defining illnesses, including Kaposi's sarcoma (KS). We used observational data from the Multicenter AIDS Cohort Study (MACS) to estimate the effect of zidovudine use on the subsequent incidence of KS. To do this, we examined and adjusted for predictors of zidovudine use. CD4 lymphocyte counts, the development of HIV-related symptoms and AIDS, and changes in these factors were important predictors of zidovudine use. We used these associations to control for confounding by these and other factors with the G-estimation approach. We found no evidence that zidovudine use affected the time to KS in the MACS; the point estimate (95% confidence interval [CI]) for increase in time to KS was zero (-28%-68%). The relative risk was 1.0 (95% CI, 0.54-1.84). Randomized trials suggest that zidovudine may prevent KS. We discuss possible explanations for differences between results.

Background and aim The association of HIV with coronary atherosclerosis has been established; however, the progression of coronary atherosclerosis over time among participants with HIV is not well known. The Multicenter AIDS Cohort Study Quantitative Coronary Plaque Progression Study is a large prospective multicenter study quantifying progression of coronary plaque assessed by serial coronary computed tomography angiography (CTA). Patients and methods HIV-infected and uninfected men who were enrolled in the Multicenter AIDS Cohort Study Cardiovascular Substudy were eligible to complete a follow-up contrast coronary CTA 3–6 years after baseline. We measured coronary plaque volume and characteristics (calcified and noncalcified plaque including fibrous, fibrous-fatty, and low attenuation) and vulnerable plaque among HIV-infected and uninfected men using semiautomated plaque software to investigate the progression of coronary atherosclerosis over time. Conclusion We describe a novel, large prospective multicenter study investigating incidence, transition of characteristics, and progression in coronary atherosclerosis quantitatively assessed by serial coronary CTAs among HIV-infected and uninfected men.

Objectives The aim of the study was to characterize contemporary patterns and correlates of testosterone therapy (TTh) use and discontinuation by HIV serostatus among men in the Multicenter AIDS Cohort Study (MACS). Methods Self‐reported testosterone use data were collected semiannually from 2400 (1286 HIV‐infected and 1114 HIV‐uninfected) men who have sex with men. Multivariable Poisson regression was used to estimate prevalence ratios for TTh use and predictors of TTh discontinuation (2012–2015). Results Use was higher among HIV‐infected compared with HIV‐uninfected men in all age strata, with an age‐adjusted prevalence of 17% vs . 5%, respectively (adjusted prevalence ratio 3.7; P &lt; 0.001). Correlates of use in the multivariable model were similar by HIV serostatus: white race, the Los Angeles (LA) site, more than one recent sexual partner, non‐smoking status, and higher American Heart Association/American College of Cardiology (AHA/ACC) cardiovascular disease (CVD) risk score category (approximately 70% of testosterone users were in the high‐risk category). Compared with HIV‐uninfected men, HIV‐infected men more frequently reported building muscle mass as a motivation for testosterone use. The TTh discontinuation rate was 20.9/100 person‐years [95% confidence interval (CI) 17.3, 25.0/100 person‐years]. Relative to HIV‐uninfected men, HIV‐infected men were half as likely to discontinue (adjusted incidence rate ratio 0.4; P &lt; 0.001). Discontinuation was 40% higher in the period after the US Food and Drug Administration (FDA) safety communication for testosterone in 2014, independent of co‐factors ( P = 0.06). Conclusions Given the high prevalence of both TTh use and CVD risk among HIV‐infected men, the benefits and risks of TTh should be examined in future studies of aging HIV‐infected men and monitored routinely in clinical practice.

HIV infection has been associated with diastolic heart failure and atrial fibrillation. The purpose of this study is to determine whether HIV infection is associated with differences in left ventricular mass (LVM), left ventricular end-diastolic volume (LVEDV), and left atrial volume (LAV) indexed to body surface area (left ventricular mass index, left ventricular end-diastolic volume index [LVEDVI], and left atrial volume index [LAVI], respectively). Cross-sectional study of 721 men [425 HIV-infected (HIV+), 296 HIV-uninfected (HIV−) enrolled in the cardiovascular substudy of the Multicenter AIDS Cohort Study (MACS). Participants underwent cardiac computed tomography imaging. A blinded reader measured LVM, LVEDV, and LAV. We used multivariable linear regression models to evaluate whether LVEDVI, left ventricular mass index (LVMI), and LAVI differed by HIV serostatus, adjusting for demographics and cardiovascular disease risk factors. LVMI was significantly greater in HIV+ compared with HIV− men, with adjusted difference of 2.65 g/m2 (95% confidence interval 0.53–4.77, p < .001). Left ventricular end-diastolic index and LAVI did not differ significantly between the two groups. HIV-related factors (nadir CD4 count, clinical AIDS diagnosis, cumulative antiretroviral therapy use, and cumulative protease inhibitor use) were not significantly associated with LVMI, LVEDVI, or LAVI. LVM was significantly higher in HIV+ than HIV− men, which may contribute to the observed increased risk for diastolic heart failure associated with HIV infection. Although HIV infection has been associated with an increased risk for atrial fibrillation, we did not find any difference in LAV by HIV serostatus.

Objective: The aim of this study was to assess the association of cardiovascular disease (CVD) risk scores and coronary artery plaque (CAP) progression in HIV-infected participants. Methods: We studied men with and without HIV-infection enrolled in the Multicenter AIDS Cohort Study (MACS) CVD study. CAP at baseline and follow-up was assessed with cardiac computed tomography angiography (CCTA). We examined the association between baseline risk scores including pooled cohort equation (PCE), Framingham risk score (FRS), and Data collect of Adverse effects of anti-HIV drugs equation (D:A:D) and CAP progression. Results: We studied 495 men (211 HIV-uninfected, 284 HIV-infected). The adjusted odds ratio (aOR) of total plaque volume (TPV) and noncalcified plaque volume (NCPV) progression in the highest relative to lowest tertile was 9.4 [95% confidence interval (95% CI) 2.4–12.1, P &lt; 0.001)] and 7.7 (95% CI 3.1–19.1, P &lt; 0.001) times greater, respectively, among HIV-uninfected men in the PCE atherosclerotic cardiovascular disease (ASCVD) high vs. low-risk category. Among HIV-infected men, the association for TPV and NCPV progression for the same PCE risk categories, odds ratio (OR) 2.8 (95% CI 1.4–5.8, P &lt; 0.01) and OR 2.4 (95% CI 1.2–4.8, P &lt; 0.05), respectively ( P values for interaction by HIV = 0.02 and 0.08, respectively). Similar results were seen for the FRS risk scores. Among HIV-uninfected men, PCE high risk category identified the highest proportion of men with plaque progression in the highest tertile, although in HIV-infected men, high-risk category by D:A:D identified the greatest percentage of men with plaque progression albeit with lower specificity than FRS and PCE. Conclusion: PCE and FRS categories predict CAP progression better in HIV-uninfected than in HIV-infected men. Improved CVD risk scores are needed to identify high-risk HIV-infected men for more aggressive CVD risk prevention strategies.

Patients with AIDS in the late stages of disease can develop dementia. Previous studies have suggested HIV encephalitis is the pathological substrate of HIV-associated dementia. We hypothesized that patients who survive longer after the initial diagnosis of AIDS would have a higher brain HIV burden and consequently manifest dementia. We examined the relationship between length of survival after AIDS diagnosis and the presence of HIV encephalitis or HIV-associated dementia. We studied retrospectively the following parameters in 74 consecutive AIDS autopsies: length of survival after AIDS diagnosis, clinical diagnosis of dementia, and neuropathologic findings (including HIV burden assessment). Multinucleated giant cells (MNGC) were identified in 20% of the brains studied. HIV gp41 was detected by immunocytochemistry in 54%, approximately half of which had abundant HIV burden. Brains from all 4 patients who were clinically diagnosed with dementia and had no opportunistic neuropathologic changes contained MNGC and abundant HIV burden. Survival after AIDS diagnosis was significantly longer in patients with MNGC (p = 0.03) or abundant HIV burden (p = 0.02). A trend toward longer survival after AIDS diagnosis was apparent in patients with dementia, but did not reach statistical significance. These findings suggest that prolonged survival with immunosuppression may be a prerequisite for the development of HIV encephalitis.