Cytomegalovirus Viremia, Mortality, and End-Organ Disease Among Patients With AIDS Receiving Potent Antiretroviral Therapies

Abstract

To determine the association of cytomegalovirus (CMV) viremia with CMV disease and death in patients with AIDS. Prospective, observational cohort study conducted at a university hospital. A cohort of 190 subjects with AIDS who were CMV seropositive and had no history or evidence of CMV disease were longitudinally evaluated for signs and symptoms of CMV disease and CMV viremia with plasma CMV DNA polymerase chain reaction (PCR) and whole blood CMV hybrid capture. A total of 187 subjects had at least 1 study visit following entry. At baseline, the median CD4 cell count and plasma HIV RNA level were 110/microL (range = 3-620/microL) and 47,973 copies/mL (<30- >750,000 copies/mL), respectively. Highly active antiretroviral therapy (HAART) use increased from 87.5% during the 1st study year to 98.5% by the end of the study. During a median follow-up of 334 days, 16% (30) of the subjects died and 2 (6%) developed CMV disease. No deaths were attributable to CMV disease; 4 subjects who died developed CMV prior to death. Baseline HIV viral load and final CD4 cell count were significantly and independently associated with mortality. Detectable plasma CMV DNA PCR was an independent predictor of death even after adjusting for HIV RNA level and CD4 cell count prior to death (P = 0.038). In contrast, whole blood CMV hybrid capture did not predict mortality. The CMV assays neither collectively nor individually were found to be associated with the few cases of CMV disease. In patients with AIDS and seropositive for CMV, detection of CMV viremia with plasma CMV DNA PCR was predictive of death and provided additional prognostic information on the risk of all cause-mortality beyond that obtained with CD4 cell count and HIV viral load testing alone. Detection of CMV viremia by plasma with CMV DNA PCR in patients with AIDS, particularly those with low CD4 cell counts, provides additional rationale for optimization of antiretroviral therapy and consideration for preemptive anti-CMV therapy.