Abstract:
Background—Well-tolerated medications that slow HIV-1 disease progression and delay initiation
of antiretroviral therapy (ART) are needed. Most HIV-1-infected persons are dually-infected with
herpes simplex virus type 2 (HSV-2). Daily HSV-2 suppression reduces plasma HIV-1 levels, but
whether HSV-2 suppression delays HIV-1 disease progression is unknown.
Methods—Within a randomized, placebo-controlled trial of HSV-2 suppressive therapy (acyclovir
400 mg orally bid) to decrease HIV-1 transmission, 3381 HSV-2/HIV-1 dually-infected heterosexual
Africans who at enrollment had CD4 counts ≥250 cells/mm 3 and were not taking ART were followed
for up to 24 months. We evaluated the effect of acyclovir on HIV-1 disease progression, defined by
a primary composite endpoint of first occurrence of CD4 count <200 cells/mm 3 , ART initiation, or
non-trauma related death. As an exploratory analysis, we evaluated the endpoint of CD4 decline to
<350 cells/mm 3 .
Findings—At enrollment, median CD4 was 462 cells/mm 3 and median HIV-1 plasma RNA was
4.1 log 10 copies/mL. Acyclovir reduced risk of HIV-1 disease progression: 284 participants on
acyclovir versus 324 on placebo reached the primary endpoint (hazard ratio [HR] 0.84, 95%
confidence interval [CI] 0.71–0.98, p=0.03). Among participants with CD4 counts ≥350 cells/
mm 3 , acyclovir delayed risk of CD4 decline to <350 cells/mm 3 (HR 0.81, 95% CI 0.71–0.93,
p=0.002).
Interpretation—HSV-2 suppression with acyclovir reduced the risk of HIV-1 disease progression
by 16% (95% CI 2–29%). The role of HSV-2 suppression in reducing HIV-1 disease progression
prior to ART initiation warrants consideration (ClinicalTrials.gov #NCT00194519)
