Daily Oral Tenofovir and Emtricitabine–Tenofovir Preexposure Prophylaxis Reduces Herpes Simplex Virus Type 2 Acquisition Among Heterosexual HIV-1–Uninfected Men and Women

Original Research1 July 2014Daily Oral Tenofovir and Emtricitabine–Tenofovir Preexposure Prophylaxis Reduces Herpes Simplex Virus Type 2 Acquisition Among Heterosexual HIV-1–Uninfected Men and WomenA Subgroup Analysis of a Randomized TrialConnie Celum, MD, MPH, Rhoda A. Morrow, PhD, Deborah Donnell, PhD, Ting Hong, MD, PhD, Craig W. Hendrix, MD, PhD, Katherine K. Thomas, MS, Kenneth H. Fife, MD, PhD, Edith Nakku-Joloba, MBChB, PhD, Andrew Mujugira, MBChB, MPH, and Jared M. Baeten, MD, PhD, for the Partners PrEP Study Team*Connie Celum, MD, MPHFrom University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington; Johns Hopkins University, Baltimore, Maryland; Indiana University, Indianapolis, Indiana; and Makerere University, Kampala, Uganda.Search for more papers by this author, Rhoda A. Morrow, PhDFrom University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington; Johns Hopkins University, Baltimore, Maryland; Indiana University, Indianapolis, Indiana; and Makerere University, Kampala, Uganda.Search for more papers by this author, Deborah Donnell, PhDFrom University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington; Johns Hopkins University, Baltimore, Maryland; Indiana University, Indianapolis, Indiana; and Makerere University, Kampala, Uganda.Search for more papers by this author, Ting Hong, MD, PhDFrom University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington; Johns Hopkins University, Baltimore, Maryland; Indiana University, Indianapolis, Indiana; and Makerere University, Kampala, Uganda.Search for more papers by this author, Craig W. Hendrix, MD, PhDFrom University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington; Johns Hopkins University, Baltimore, Maryland; Indiana University, Indianapolis, Indiana; and Makerere University, Kampala, Uganda.Search for more papers by this author, Katherine K. Thomas, MSFrom University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington; Johns Hopkins University, Baltimore, Maryland; Indiana University, Indianapolis, Indiana; and Makerere University, Kampala, Uganda.Search for more papers by this author, Kenneth H. Fife, MD, PhDFrom University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington; Johns Hopkins University, Baltimore, Maryland; Indiana University, Indianapolis, Indiana; and Makerere University, Kampala, Uganda.Search for more papers by this author, Edith Nakku-Joloba, MBChB, PhDFrom University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington; Johns Hopkins University, Baltimore, Maryland; Indiana University, Indianapolis, Indiana; and Makerere University, Kampala, Uganda.Search for more papers by this author, Andrew Mujugira, MBChB, MPHFrom University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington; Johns Hopkins University, Baltimore, Maryland; Indiana University, Indianapolis, Indiana; and Makerere University, Kampala, Uganda.Search for more papers by this author, and Jared M. Baeten, MD, PhDFrom University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington; Johns Hopkins University, Baltimore, Maryland; Indiana University, Indianapolis, Indiana; and Makerere University, Kampala, Uganda.Search for more papers by this author, for the Partners PrEP Study Team*Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M13-2471 SectionsSupplemental MaterialAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail AbstractThis article has been corrected. The original version (PDF) is appended to this article as a Supplement.AbstractBackground:Daily oral preexposure prophylaxis (PrEP) using the antiretroviral tenofovir disoproxil fumarate (TDF) alone or in combination with emtricitabine (FTC–TDF) reduces the risk for HIV-1 acquisition. Tenofovir has in vitro activity against herpes simplex virus type 2 (HSV-2).Objective:To assess the efficacy of daily oral PrEP with tenofovir and FTC–TDF in the prevention of HSV-2 acquisition.Design:Subgroup analysis of data from a randomized, placebo-controlled trial with concealed allocation. (ClinicalTrials.gov: NCT00557245)Setting:Multiple sites in Kenya and Uganda.Participants:Heterosexual men and women who were seronegative for HIV-1 and HSV-2 and at high risk for HIV-1 acquisition due to having an HIV-1–infected partner.Intervention:Once-daily oral tenofovir disoproxil fumarate (TDF), alone or combined with emtricitabine (FTC-TDF), compared with placebo.Measurements:HSV-2 seroconversion.Results:A total of 131 participants seroconverted to HSV-2 (79 of 1041 assigned to tenofovir or FTC–TDF PrEP [HSV-2 incidence, 5.6 per 100 person-years] and 52 of 481 assigned to placebo [HSV-2 incidence, 7.7 per 100 person-years]). The hazard ratio (HR) for HSV-2 acquisition with daily oral PrEP was 0.70 (95% CI, 0.49 to 0.99; P = 0.047) compared with placebo, and the absolute risk reduction was 2.1 per 100 person-years. Among the 1044 participants with HSV-2–infected partners, the HR for PrEP was 0.67 (CI, 0.46 to 0.98; P = 0.038) compared with placebo, and the absolute risk reduction was 3.1 per 100 person-years.Limitation:Randomization was not stratified by HSV-2 status, and diagnostic tests to exclude participants with acute HSV-2 at baseline are not available.Conclusion:Daily oral tenofovir-based PrEP significantly reduced the risk for HSV-2 acquisition among heterosexual men and women. Modest protection against HSV-2 is an added benefit of HIV-1 prevention with oral tenofovir-based PrEP.Primary Funding Source:Bill & Melinda Gates Foundation.References1. Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L, et al; iPrEx Study Team. 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Watson-Jones D, Weiss HA, Rusizoka M, Changalucha J, Baisley K, Mugeye K, et al; HSV trial team. Effect of herpes simplex suppression on incidence of HIV among women in Tanzania. N Engl J Med. 2008;358:1560-71. [PMID: 18337596] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAuthors: Connie Celum, MD, MPH; Rhoda A. Morrow, PhD; Deborah Donnell, PhD; Ting Hong, MD, PhD; Craig W. Hendrix, MD, PhD; Katherine K. Thomas, MS; Kenneth H. Fife, MD, PhD; Edith Nakku-Joloba, MBChB, PhD; Andrew Mujugira, MBChB, MPH; Jared M. Baeten, MD, PhDAffiliations: From University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington; Johns Hopkins University, Baltimore, Maryland; Indiana University, Indianapolis, Indiana; and Makerere University, Kampala, Uganda.Note: All authors vouch for the completeness and accuracy of the data presented.Acknowledgment: The authors thank the study participants and the study team.Grant Support: By the Bill & Melinda Gates Foundation (OOP47674).Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-2471.Reproducible Research Statement: Study protocol and statistical code: Available from Dr. Celum (e-mail, [email protected]edu). Data set: Portions of the analytic data set are available to approved individuals through written agreement with Dr. Celum (e-mail, [email protected]edu).Corresponding Author: Connie Celum, MD, MPH, University of Washington, 325 Ninth Avenue, UW Box 359927, Seattle, WA 98104.Current Author Addresses: Drs. Celum, Donnell, Hong, and Baeten; Ms. Thomas; and Mr. Mujugira: University of Washington, 325 Ninth Avenue, UW Box 359927, Seattle, WA 98104.Dr. Morrow: Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, LE-500, Seattle, WA 98109.Dr. Hendrix: Department of Medicine, Johns Hopkins University, 600 North Wolfe Street, Harvey 502, Baltimore, MD 21287-5554.Dr. Fife: Department of Medicine, Indiana University, Emerson H/Room 435, 545 Barnhill Drive, Indianapolis, IN 46202.Dr. Nakku-Joloba: School of Public Health, Makerere University, PO Box 22418, Plot 106, Block 213, Bukoto, Kampala, Uganda.Author Contributions: Conception and design: C. Celum, D. Donnell, J.M. Baeten.Analysis and interpretation of the data: C. Celum, R.A. Morrow, D. Donnell, T. Hong, C.W. Hendrix, K.K. Thomas, K.H. Fife, J.M. Baeten.Drafting of the article: C. Celum, D. Donnell, J.M. Baeten.Critical revision of the article for important intellectual content: C. Celum, D. Donnell, K.H. Fife, E. Nakku-Joloba, J.M. Baeten.Final approval of the article: C. Celum, R.A. Morrow, D. Donnell, C.W. Hendrix, K.H. Fife, E. Nakku-Joloba, A. Mujugira, J.M. Baeten.Provision of study materials or patients: K.H. Fife, A. Mujugira, J.M. Baeten.Statistical expertise: D. Donnell, T. Hong, K.K. Thomas.Obtaining of funding: C. Celum, J.M. Baeten.Administrative, technical, or logistic support: E. Nakku-Joloba, A. Mujugira, J.M. Baeten.Collection and assembly of data: C. Celum, R.A. Morrow, D. Donnell, C.W. Hendrix, K.H. Fife, E. Nakku-Joloba, A. Mujugira, J.M. Baeten.* For a list of the members of the Partners PrEP Study Team, see the Appendix. 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Cost-Effectiveness of Pre-Exposure Prophylaxis to Reduce HIV-1 and HSV-2 Incidence in HIV-Serodiscordant Couples in South AfricaMultipurpose prevention technologies for reproductive and sexual health 1 July 2014Volume 161, Issue 1Page: 11-19KeywordsAttentionBlood plasmaDrugsHIV-1Herpes simplexHeterosexualsPreexposure prophylaxisPregnancyRandomized trialsResearch laboratories ePublished: 1 July 2014 Issue Published: 1 July 2014 Copyright & PermissionsCopyright © 2014 by American College of Physicians. 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