Coronavirus infection in an AIDS patient

A 30-year-old Chinese man presented in April 2003 to a public hospital in Hong Kong for suspected severe acute respiratory syndrome (SARS). He had been living with HIV (currently at stage CIII) for 5 years and was on highly active antiretroviral therapy (HAART) comprising abacavir 300 mg twice a day, efavirenz 600 mg at night, Kaletra 4 capsules (each capsule contains lopinavir 133.3 mg and ritonavir 33.3 mg) and tenofovir 300 mg twice a day, plus standard Pneumocystis carinii pneumonia prophylaxis. He had been on the present HAART regimen since November 2002 and had good drug adherence. His CD4 cell count and viral load were 134 cells/μl and 470 copies/ml [by reverse transcriptase–polymerase chain reaction (PCR), Roche Amplicor], respectively, in February 2003. The patient gave a one-week history of right-sided chest pain and chills, followed by fever, increasing dry cough and malaise. On admission, he had a fever of 38°C, was mildly tachypnoeic; and his blood pressure was 155/77 mmHg, with a pulse rate of 90/min. The pulse oximetry read 97% while on oxygen 3 l/min. There was no added sound on chest examination. Chest X-ray showed haziness in the right lower zone, with the costophrenic angle being sharp, compatible with consolidation. His white cell count was 6.1 × 109/l, with a significant lymphopenia of 0.4 × 109/l compared with that of 1.2 × 109/l recorded 2 months earlier. Renal and liver function tests, clotting times and creatine kinase level were within normal limits. He was started on pipercillin/tazobactam for empirical treatment of his pneumonia. His fever subsided 24 h later, with a gradual improvement of chest symptoms. His sputum culture revealed commensal organisms only. A work-up for pneumonia, including sputum Gram stain and culture, acid-fast bacilli smear, nasal and throat swabs for the usual viral pathogens did not reveal positive results. His lymphocyte count rose to 1.0 on day 9. Because of the concurrent SARS outbreak in Hong Kong, a throat swab was taken on day 2 for coronavirus using PCR, which subsequently showed a positive result. The patient was commenced on ribavirin 1200 mg three times a day and prednisolone 25 mg three times a day by mouth from day 7 according to the hospital's standard protocol [1]. He was also covered with lamivudine, to prevent hepatitis flare in view of his hepatitis B surface antigen-positive status. Ribavirin was continued for a total of 20 days, whereas steroid was tailed off over 4 weeks. He tolerated the treatment and remained asymptomatic until day 25 when the fever relapsed (see Fig. 1) and a chest X-ray showed increased right lower zone haziness. Two sputum smears for acid-fast bacilli were positive (taken on days 29 and 30). He was started on anti-tuberculosis treatment and his fever subsided after one day. The first antibodies test for coronavirus on admission was negative, whereas the second titre taken 2 weeks after the onset of symptoms was 1 : 40. Coronavirus PCR tests were repeated for throat and nasal swabs, stool and urine on day 39 and were negative.Fig. 1.: Temperature of patient. A: Day 1 – patient was started on piperacillin/tazobactam; before admission, patient was given kaletra, abacavir, efavirenz, tenofovir and septrin. B: Day 8 – patient was started on ribavirin, prednisolone and lamivudine. C: Day 25 – patient had recurrence of fever. D: Day 26 – patient was started on anti-tuberculosis medication.This is the first reported case of SARS in an HIV-infected patient. The diagnosis of SARS was made clinically, supported by lymphopenia, positive PCR and serology for SARS-associated coronavirus. Our patient ran a relatively mild course despite his immunocompromised state. There are two possible reasons for this observation. First, the HAART regimen might have protective antiviral effects during the viraemic phase. Kaletra has been found to have some in-vitro activities against coronavirus, and was used as an experimental treatment agent in some hospitals in Hong Kong. The dose of Kaletra used for such purposes was 500 mg twice a day. The viral main proteinase 3CLpro was found to control the activities of the coronavirus replication complex [2]. It is unknown whether Kaletra, a combined protease inhibitor, acts on similar targets. Second, the he grave prognognosis in young patients with SARS might be related to the excessive immune response to the new virus. Cytokine dysregulation may account, at least partly, for the severity of clinical disease [3]. The defective cellular immunity in HIV infection could paradoxically be a protective factor in some patients. The plausibility of these explanations has yet to be confirmed. On the other hand, it could be argued that if Kaletra was active against coronavirus, it should have prevented the infection in the first place. Finally, HIV and coronavirus co-infection may carry other deleterious consequences. The precipitation of tuberculosis by steroid is a cause for concern [4]. There is also the potential risk of prolonged viral shedding in HIV infection if the clearance of coronavirus is ineffective. Furthermore, the mild symptoms of SARS in HIV patients may go unnoticed, making public health control of SARS difficult. Acknowledgement The authors would like to thank the staff of the Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong, for their selfless and heroic devotion in the management of patients with SARS in Hong Kong, despite the potential threat to their lives and those of their families.