Daily Acyclovir Delays HIV-1 Disease Progression Among HIV-1/ HSV-2 Dually-Infected Persons: A Randomized Trial
Jairam, R. Lingappa; Jared, M. Baeten; Anna, Wald; James, P. Hughes; Katherine, K. Thomas; Andrew, Mujugira; Nelly, Mugo; Elizabeth, A. Bukusi; Craig R., Cohen; Elly, Katabira; Allan, Ronald; James, Kiarie; Carey, Farquhar; Grace, John Stewart; Joseph, Makhema; Myron, Essex; Edwin, Were; Kenneth, H. Fife; Guy de, Bruyn; Glenda, E. Gray; James, McIntyre; Rachel, Manongi; Saidi, Kapiga; David, Coetzee; Susan, Allen; Mubiana, Inambao; Kayitesi, Kayitenkore; Etienne, Karita; William, Kanweka; Sinead, Delany; Helen, Rees; Bellington, Vwalika; Amalia, Magaret; Richard S., Wang; Lara, Kidoguchi; Linda, Barnes; Renee, Ridzon; Lawrence, Corey; Connie, Celum
Date:
2010-05-05
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/mm3 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/mm3, ART initiation, or
non-trauma related death. As an exploratory analysis, we evaluated the endpoint of CD4 decline to
<350 cells/mm3.
Findings—At enrollment, median CD4 was 462 cells/mm3 and median HIV-1 plasma RNA was
4.1 log10 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/
mm3, acyclovir delayed risk of CD4 decline to <350 cells/mm3 (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
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