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http://ir.mu.ac.ke:8080/jspui/handle/123456789/937
Title: | Daily Acyclovir Delays HIV-1 Disease Progression Among HIV-1/ HSV-2 Dually-Infected Persons: A Randomized Trial |
Authors: | 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 |
Keywords: | HIV-1 disease progression HIV-1 discordant couples HSV-2; genital herpes herpes suppression acyclovir; randomized clinical trial |
Issue Date: | 5-May-2010 |
Publisher: | NIH Lancet public access |
Series/Report no.: | doi:10.1016/S0140-6736(09)62038-9.; |
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 |
URI: | http://ir.mu.ac.ke:8080/xmlui/handle/123456789/937 |
Appears in Collections: | School of Medicine |
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aids 2.pdf | 1.23 MB | Adobe PDF | View/Open |
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