Impact of aciclovir on genital and plasma HIV-1 RNA in HSV-2/HIV-1 co-infected women: A randomized placebo-controlled trial in South Africa
Reproductive Health and HIV Research Unit, University of Witwatersrand, Johannesburg, South Africa; Clinical Research Unit and Medical Statistics Unit, London School of Hygiene and Tropical Medicine, London, United Kingdom; Department of Molecular Medicine and Haematology, University of Witwatersrand, Johannesburg, South Africa; Laboratoire de Microbiologie, Hôpital Saint-Louis, France; Université Paris V, Centres de Recherches Biomédicales des Cordeliers and Laboratoire de Virologie, Hôpital Européen Georges Pompidou, Paris, France; Reproductive Health and HIV Research Unit, University of the Witwatersrand, PO Box 18512, Hillbrow, Johannesburg 2038, South Africa
Background: Several studies suggest that herpes simplex virus type 2 (HSV-2) may enhance HIV-1 transmission and disease progression. Methods: We conducted a randomized, double-blind, placebo-controlled trial of aciclovir 400 mg twice daily for 3 months in 300 HSV-2/HIV-1 co-infected women not yet on highly active antiretroviral therapy (HAART). Participants were evaluated prerandomization and at monthly visits for 3 months. Primary outcomes were the detection and quantity of genital HIV-1 RNA at the month 3 (M3) visit. Analyses were also undertaken using data from all visits. The treatment effects on plasma HIV-1 RNA, CD4 + cell count and genital HSV-2 DNA were also assessed. Results: At M3 fewer women had detectable genital HIV in the aciclovir group compared to placebo, but this was not significant [61/132 (46%) vs. 71/137 (52%), risk ratio (RR) 0.89, 95% confidence interval (CI) 0.70-1.14; P = 0.36]. There was also little difference in quantity of HIV-1 RNA among shedders(+0.13 log 10 copies/ml, 95% CI -0.14 to 0.39) at M3. However, aciclovir significantly decreased the frequency of HIV-1 shedding over all visits [adjusted odds ratio (OR) 0.57, 95% CI 0.36-0.89]. Significant reductions in M3 plasma HIV-1 RNA (-0.34 log 10 copies/ml, 95% CI 0.15-0.54), genital HSV-2 DNA (8 vs. 20%, RR 0.37, 95% CI 0.19-0.73) and genital ulceration (8 vs. 18%, RR 0.43, 95% CI 0.22-0.84) were observed in the aciclovir group. Conclusion: HSV-2 suppressive therapy, by reducing HIV-1 plasma viral load and altering the pattern of genital HIV-1 shedding, may contribute to the reduction in sexual transmission of HIV-1 and may delay the requirement for HAART initiation. © 2009 Wolters Kluwer Health|Lippincott Williams & Wilkins.
aciclovir; placebo; virus DNA; virus RNA; adult; article; CD4 lymphocyte count; clinical trial; concurrent infection; controlled clinical trial; controlled study; disease course; double blind procedure; drug efficacy; female; genital herpes; genital ulcer; Herpes simplex virus 2; human; Human immunodeficiency virus 1; Human immunodeficiency virus infection; major clinical study; priority journal; randomized controlled trial; treatment outcome; virus transmission; Acyclovir; Adult; Antiviral Agents; CD4 Lymphocyte Count; Cervix Uteri; DNA, Viral; Double-Blind Method; Female; Follow-Up Studies; Herpes Genitalis; Herpesvirus 2, Human; HIV Infections; HIV-1; Humans; Middle Aged; RNA, Viral; Sexual Behavior; Specimen Handling; Treatment Outcome; Vagina; Virus Shedding; Young Adult