789 CMV Viremia is Predictive of Death Among Persons with AIDS Independent of Plasma HIV RNA Level and CD4+ Cell Count D. A. Wohl*1, A. Weinberg2, D. Zeng1, S. Fiscus1, N. Glomb1, T. Alcorn3, R. Pilson4, C. V. der Horst1 1Univ of North Carolina, Chapel Hill; 2Univ of Colorado Hlth Sci Ctr, Denver; 3Lab Corp of America, Research Triangle Park, NC; and 4Roche Labs, Nutley, NJ
Background: Detection of CMV viremia has been associated with development and relapse of CMV end-organ disease (EOD). The relationship between CMV viremia and mortality among patients (pts) with AIDS has not been determined.
Methods: Prospective observational study; 200 HIV+ pts with a CD4+ count < 200 cells/ul at entry or ever < 50 cells/ul and no evidence of CMV EOD by ophthalmoscopy and physical examination were enrolled 6/97-1/02. Blood was collected at clinic visits for plasma CMV DNA PCR (Roche), whole blood CMV DNA hybrid capture (Digene), pp67 NucliSens (bioMerieux), and pp65 antigenemia. Ophthalmologic exams and surveys for extra-ocular CMV disease were conducted every 3-6 months based on CD4+ count strata. Cox proportional hazard regression models were used to determine the independent effects of CMV viremia assays, plasma HIV-1 RNA, and CD4+ count on survival. Data on the 187 subjects with at least 2 study visits are presented.
Results: Median on study follow-up was 410 days. Of the cohort, 75% were male and 67% were non-white. Median age was 39 yrs. Median entry CD4+ count and HIV-1 RNA level were 113 cells/ul and 43,950 copies/mL, respectively. The rate of mortality during the study was 16% (30 subjects). None of the deaths were attributed to CMV EOD. A diagnosis of CMV EOD was made prior to death in 4 subjects (all retinitis). Two (2) additional subjects developed CMV retinitis and remain alive. Baseline plasma HIV-1 RNA level, but not CD4+ count, was associated with risk of death with a 66% increased risk of death for each log increase in HIV viral load (p = 0.041). Adjusting for baseline variables including HIV-1 RNA and CD4+ count, subjects with detectable CMV DNA PCR at last evaluation were 1.9 times more likely to die than those with undetectable results (p = 0.0011). There was a trend for increased mortality among subjects with CMV viremia detected by hybrid capture with a 70% increased risk of death (p = 0.08). No subjects who died had CMV viremia detected by NucliSens or antigenemia at their final study evaluation.
Conclusions: CMV viremia as detected by plasma CMV DNA PCR was independently associated with death among pts with AIDS even when death was not described to be CMV-related. CMV viremia was more predictive of death than HIV viremia. Whether pre-emptive, anti-CMV therapy in persons with AIDS and CMV viremia will reduce mortality needs to be determined.
