Objectives: To document the natural history of herpes simplex virus type 2 (HSV-2) in relation to HIV and highly active antiretroviral therapy (HAART) in Africa, a longitudinal study was conducted of women in the placebo arms of two randomised controlled trials of HSV-suppressive therapy in Burkina Faso.
Methods: 22 HIV-uninfected women (group 1), 30 HIV-1-infected women taking HAART (group 2), and 68 HIV-1-infected women not eligible for HAART (group 3) were followed over 24 weeks. HSV-2 DNA was detected on alternate weeks using real-time PCR from cervicovaginal lavages. Plasma HIV-1 RNA was measured every month. CD4 cell counts were measured at enrolment.
Results: Ulcers occurred on 1.9%, 3.1% and 7.2% of visits in groups 1, 2 and 3 (p = 0.02). Cervicovaginal HSV-2 DNA was detected in 45.5%, 63.3% and 67.6% of women (p = 0.11), and on 4.3%, 9.7% and 15.5% of visits in the three groups (p<0.001). Among HIV-infected women, cervicovaginal HSV-2 DNA was detected more frequently during ulcer episodes (adjusted risk ratio (aRR) 2.79, 95% CI 2.01 to 3.86) and less frequently among women practising vaginal douching (aRR 0.60, 95% CI 0.40 to 0.91). Compared with women not taking HAART and with CD4 cell counts of 500 cells/μl or greater, women on HAART had a similar risk of HSV-2 shedding (aRR 0.95, 95% CI 0.52 to 1.73), whereas women with CD4 cell counts of 200–500 cells/μl were more likely to shed HSV-2 (aRR 1.71, 95% CI 1.02 to 2.86).
Conclusions: HSV-2 reactivations occur more frequently among HIV-infected women, particularly those with low CD4 cell counts, and are only partly reduced by HAART. HSV therapy may benefit HIV-infected individuals during HAART.
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Funding: This study was sponsored by France’s Agence Nationale de Recherches sur le SIDA et les Hépatites (ANRS), grants ANRS-1291 and ANRS-1285. Additional financial support was provided through the UK’s Department for International Development (DFID)-funded Knowledge Programme on HIV/AIDS and STI of the London School of Hygiene and Tropical Medicine.
Competing interests: None declared.
Ethics approval: The research protocol was approved by the institutional review board at Centre Muraz, and by the research ethics committees at the Burkina Faso Ministry of Health and at the London School of Hygiene and Tropical Medicine. The trials were registered with the International Clinical Trials Registers (NCT00158509). Eligible women provided witnessed written (or thumb-printed) consent. Study procedures complied with the principles of the Helsinki Declaration and the ANRS Research Ethics Charter.
Contributors: PM, NN, HAW and PVP conceived the study, which was carried out by NN, IK, AO and AS. Laboratory analyses were performed by MCD in Bobo Dioulasso and VF and MS in Montpellier. Statistical analyses were performed by NN and HAW and reviewed by PM. The first manuscript was drafted by PM and NN with inputs and reviews from all co-authors who approved the final version of the manuscript.
Composition of the ANRS 1285 Study Group: Eloi Bahembera, Abdramane Berthé, Minata Coulibaly, Marie-Christine Defer, Ramata Diallo, Didier Djagbaré, Issouf Konaté, Florent Ky-Dama, Gilles T M’Boutiki, Nicolas Méda, Inès Millogo, Nicolas Nagot, Abdoulaye Ouedraogo, Djénéba Ouedraogo, Francois Rouet, Anselme Sanon, Haoua Sawadogo, Roselyne Vallo and Laurence Vergne (deceased January 2007) (Centre Muraz, Bobo-Dioulasso, Burkina Faso); Philippe Mayaud, Nicolas Nagot and Helen A Weiss (London School of Hygiene and Tropical Medicine, London, UK); Pierre Becquart, Vincent Foulongne, Michel Segondy and Philippe Van de Perre, (Université Montpellier 1 and CHU Montpellier, Montpellier, France); Jean-Baptiste Andonaba and Adrien Sawadogo (University Hospital of Bobo-Dioulasso, Burkina Faso).