Baggaley R.F., Griffin J.T., Chapman R., Hollingsworth T.D., Nagot N., Delany S., Mayaud P., De Wolf F., Fraser C., Ghani A.C., Weiss H.A.
MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, United Kingdom; lnfectious Disease Epidemiology Unit, Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom; Universite Montpellier 1, EA 4205 Transmission, Pathogenese et Prevention de I'infection par le VIH, CHU Montpellier, Montpellier, France; Reproductive Health and HIV Research Unit, University of Witwatersrand, Johannesburg, South Africa; Clinical Research Unit, Department of Infectious Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom; HIV Monitoring Foundation, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands; Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, United Kingdom
Baggaley, R.F., MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, United Kingdom, Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, United Kingdom; Griffin, J.T., MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, United Kingdom; Chapman, R., lnfectious Disease Epidemiology Unit, Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom; Hollingsworth, T.D., MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, United Kingdom; Nagot, N., Universite Montpellier 1, EA 4205 Transmission, Pathogenese et Prevention de I'infection par le VIH, CHU Montpellier, Montpellier, France; Delany, S., Reproductive Health and HIV Research Unit, University of Witwatersrand, Johannesburg, South Africa; Mayaud, P., Clinical Research Unit, Department of Infectious Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom; De Wolf, F., HIV Monitoring Foundation, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands; Fraser, C., MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, United Kingdom; Ghani, A.C., MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, United Kingdom; Weiss, H.A., lnfectious Disease Epidemiology Unit, Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom
Objective: Trials of herpes simplex virus (HSV) suppressive therapy among HSV-2/ HIV-1-infected individuals have reported an impact on plasma HIV-1 viral loads (PVLs). Our aim was to estimate the population-level impact of suppressive therapy on female-to-male HIV-1 sexual transmission. Design and methods: By comparing prerandomization and postrandomization individual-level PVL data from the first two HSV suppressive therapy randomized controlled trials in sub-Saharan Africa, we estimated the effect of treatment on duration of asymptomatic infection and number of HIV-1 transmission events for each trial. Results: Assuming that a reduction in PVL is accompanied by an increased duration of HIV-1 asymptomatic infection, 4-6 years of HSV suppressive therapy produce a 1 -year increase in the duration of this stage. To avert one HIV-1 transmission requires 8.8 [95% confidence interval (Cl), 5.9-14.9] and 11.4 (95% Cl, 7.8-27.5) women to be treated from halfway through their HIV-1 asymptomatic period, using results from Burkina Faso and South African trials, respectively. Regardless of the timing of treatment initiation, 51.6 (95% Cl, 30.4-137.0) and 66.5 (95% Cl, 36.7-222.6) treatment-years are required to avert one HIV-1 infection. Distributions of set-point PVL values from sub-Saharan African populations suggest that unintended adverse consequences of therapy at the population level (i.e. increased HIV-1 transmission due to increased duration of infection) are unlikely to occur in these settings. Conclusion: HSV suppressive therapy may avert relatively few HIV-1 transmission events per person-year of treatment. Its use as a prevention intervention may be limited; however, further research into its effect on rate of CD4 cell count decline and the impact of higher dosing schedules is warranted. © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.