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Estimating the public health impact of the effect of herpes simplex virus suppressive therapy on plasma HIV-1 viral load

Baggaley, Rebecca Fa; Griffin, Jamie Ta; Chapman, Ruthb; Hollingsworth, T Déirdrea; Nagot, Nicolasc; Delany, Sineadd; Mayaud, Philippee; de Wolf, Frankf; Fraser, Christophea; Ghani, Azra Ca; Weiss, Helen Ab

doi: 10.1097/QAD.0b013e32832aadf2
Epidemiology and social

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 (CI), 5.9–14.9] and 11.4 (95% CI, 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% CI, 30.4–137.0) and 66.5 (95% CI, 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.

aMRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, UK

bInfectious Disease Epidemiology Unit, Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK

cUniversité Montpellier 1, EA 4205 Transmission, Pathogenese et Prevention de l'infection par le VIH, CHU Montpellier, Montpellier, France

dReproductive Health and HIV Research Unit, University of Witwatersrand, Johannesburg, Republic of South Africa

eClinical Research Unit, Department of Infectious Diseases, London School of Hygiene and Tropical Medicine, London, UK

fHIV Monitoring Foundation, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Received 27 November, 2008

Revised 3 February, 2009

Accepted 13 February, 2009

Correspondence to Dr Rebecca Baggaley, Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK. Tel: +44 207 5943288; e-mail: r.baggaley@imperial.ac.uk

© 2009 Lippincott Williams & Wilkins, Inc.