Deayton JR, Prof Sabin CA, Johnson MA, Emery VC, Wilson P, Griffiths PD. Lancet 2004;363:2116–2121.

BACKGROUND: Before highly active antiretroviral therapy (HAART) became available, cytomegalovirus (CMV) was a major cause of opportunistic infection in HIV-infected patients and was associated with accelerated progression to AIDS and death. We have investigated whether CMV viraemia remains a significant risk factor for progression of HIV disease and death in the era of HAART. METHODS: 374 patients whose CD4-cell count had ever been below 100 per microL were enrolled in a prospective study. Serial blood samples were tested for CMV by polymerase chain reaction (PCR). Rates of new CMV disease, new AIDS-defining disorders, and death were calculated over a median follow-up of 37 months after stratification according to baseline and most recent CMV PCR status at any point during follow-up. FINDINGS: Of 2969 PCR assays, 375 (12.6%) were positive for CMV DNA. 259 (69.3%) patients were persistently negative for CMV by PCR; 15 were persistently positive; and 100 were intermittently positive and negative. In multivariate models, CMV PCR-positive status as a time-updated covariate was significantly associated with increased relative rates of progression to a new AIDS-defining disorder (2.22 [95% CI 1.27-3.88] P=0.005) and death (4.14 [1.97-8.70] P=0.0002). INTERPRETATION: Detection of CMV in blood by PCR continues to identify patients with a poor prognosis, even in the era of HAART. Randomised controlled clinical trials of drugs active against CMV are needed to investigate whether this virus is a marker or a determinant of HIV disease progression.