Low rate of CMV end-organ disease in HIV-infected patients despite low CD4+ cell counts and CMV viremia: results of ACTG protocol A5030

Abstract

Purpose: To describe cytomegalovirus (CMV) end-organ disease (EOD) rate in AIDS patients with low CD4+ cell count despite HAART who were enrolled in a randomized, placebo-controlled trial of preemptive valganciclovir (VGCV) to prevent CMV EOD in those with CMV viremia.

Methods: Subjects (N = 338) were HIV-infected with CD4+ count <100 cells/mm3, plasma HIV RNA >400 copies/mL, and on stable or no HAART. All underwent plasma CMV DNA PCR testing every 8 weeks (Step 1); those with detectable CMV DNA were randomized to VGCV or placebo (Step 2).

Results: Plasma CMV DNA was detected in 68 (20%), of whom 4 developed CMV EOD. During Step 1, 53 died. Of the 47 who entered Step 2 (24 VGCV, 23 placebo), CMV EOD was diagnosed in 10 (4 VGCV, 6 placebo) and 15 died (7 VGCV, 8 placebo). Of those randomized to placebo, 14% were diagnosed with CMV EOD at 12 months.

Conclusions: We observed a lower CMV EOD rate among subjects receiving HAART than predicted based on published literature. However, mortality was high in this study. Our findings suggest that preemptive anti-CMV therapy in patients with persistently low CD4+ cell counts in the current treatment era may not be warranted given the low incidence of CMV EOD and high all-cause mortality observed in this study population.

Figure 1

Study design and subject disposition based on CMV viremia and EOD.