Cytomegalovirus (CMV) DNA load is an independent predictor of CMV disease and survival in advanced AIDS

Abstract

The impact of cytomegalovirus (CMV) on human immunodeficiency virus type 1 (HIV-1) disease progression has been controversial. In this study, we sought to determine if CMV viral load is independent of HIV-1 viral load in predicting CMV disease and survival. Our findings indicate that in patients with advanced AIDS, CMV DNA load is an independent marker of CMV disease and survival and is more predictive than HIV-1 RNA load. Moreover, patients who respond to preemptive therapy with oral ganciclovir, with resulting undetectable levels of CMV DNA, in their plasma, have a significantly lower risk of developing CMV disease and higher rates of survival, despite stable or increasing HIV-1 RNA loads. These data provide support for CMV as an independent risk factor for mortality in persons with advanced AIDS and further suggest that effective preemptive therapy for CMV can improve patient survival rates.

FIG. 1

Scatter plot comparing CMV DNA and HIV-1 RNA in plasma specimens obtained at baseline. CMV DNA was considered undetectable at copy numbers below 500/ml, while HIV-1 RNA was considered undetectable at copy numbers below 400/ml. r = 0.12, P = 0.0037.

FIG. 2

Multivariate logistic regression modeling of the rates of CMV disease and survival as functions of both baseline plasma CMV DNA and HIV-1 RNA loads. (A) CMV disease in placebo recipients. (B) CMV disease in ganciclovir recipients. Predicted CMV disease rates are highest among patients with high circulating levels of both CMV and HIV-1 and lowest among patients with low levels of both viruses. Although both viruses influence the CMV disease rate, plasma CMV load is a better predictor for development of disease, as indicated by the relative steepness of the logistic curve in the direction of the CMV axis. (C) Survival in placebo recipients. (D) Survival in ganciclovir recipients. Predicted death rates are highest among patients with high levels of CMV DNA and HIV-1 RNA in plasma. However, the predictive value of HIV load in this population of patients with advanced AIDS is weak compared to that of CMV load, as demonstrated by the relative steepness of the logistic curve in the direction of the CMV axis.

FIG. 3

Kaplan-Meier survival curves for study participants receiving ganciclovir who were initially plasma CMV DNA PCR positive (≥500 copies/ml) at baseline, stratified by whether they became PCR negative at 2 months. (A) Conversion from PCR-positive to PCR-negative status at 2 months, with time to the development of CMV disease shown. (B) Conversion from PCR-positive to PCR-negative status at 2 months, with time to death shown.