Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Hormonal contraception and the risk of HIV acquisition among women in South Africa Charles S. Morrison a , Stephanie Skoler-Karpoff b,c , Cynthia Kwok a , Pai-Lien Chen a , Janneke van de Wijgert c,d , Marlena Gehret-Plagianos c , Smruti Patel e , Khatija Ahmed f , Gita Ramjee g , Barbara Friedland c and Pekka Lahteenmaki c,h Objectives: To evaluate the effect of hormonal contraception including combined oral contraceptives (COCs), and the injectable progestins depo-medroxyprogesterone acetate (DMPA) and norethisterone enanthate (Net-En) on the risk of HIV acquisition among women in South Africa. Design/methods: We analyzed data from 5567 women aged 16 – 49 years participating in the Carraguard Phase 3 Efficacy Trial. Participants were interviewed about contra- ceptive use and sexual behaviors and underwent pelvic examinations and HIV testing quarterly. We used marginal structural Cox regression models to estimate the effect of hormonal contraception exposure on HIV acquisition risk among women overall and among young women (16–24 years) in particular. Results: Two hundred and seventy participants became HIV-infected (3.7 per 100 woman-years); HIV incidence was 2.8, 4.6, 3.5 and 3.4 per 100 woman-years in the COC, DMPA, Net-En and nonhormonal contraceptive groups, respectively (P ¼ 0.09). The adjusted hazard ratios (AHRs) were 0.84 [95% confidence interval (CI) 0.51 – 1.39], 1.28 (95% CI 0.92 – 1.78) and 0.92 (95% CI 0.64 – 1.32) among COC, DMPA and Net-En users, respectively, compared with the nonhormonal group controlling for covariates. Age modified the effect of hormonal contraception on HIV acquisition risk; among young women, the AHRs were 1.02 (95% CI 0.46 – 2.28) for COCs, 1.68 (95% CI 0.96 – 2.94) for DMPA and 1.36 (95% CI0.78–2.35) for Net-En users. Conclusions: In this study conducted among South African women, hormonal contra- ception did not significantly increase the risk of HIV acquisition. However, the effect estimate does not rule out a moderate increase in HIV risk associated with DMPA use found in some other recent studies. ß 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins AIDS 2012, 26:497–504 Keywords: Africa, depo-provera, heterosexual transmission, HIV acquisition, hormonal contraception, oral contraceptives, women Introduction Hormonal contraception is used by over 150 million women worldwide including over 100 million women who use combined oral contraceptives (COCs) and over 50 million who use the injectable progestin depo- medroxyprogesterone acetate (DMPA) [1]; [2]. Injectable progestin use [DMPA and norethisterone enanthate a FHI 360, Durham, North Carolina, b Memorial Sloan-Kettering Cancer Center, New York, c Population Council, New York, USA, d Academic Medical Center of the University of Amsterdam and Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands, e University of Cape Town, f University of Limpopo Medunsa Campus, g Medical Research Council, Durban, South Africa, and h University of Helsinki, Helsinki, Finland. Correspondence to Charles S. Morrison, PhD, FHI 360, Durham, NC 27713, USA. Tel: +1 919 544 7040/11472; fax: +1 919 544 7261; e-mail: cmorrison@fhi360.org Received: 13 July 2011; revised: 14 November 2011; accepted: 23 November 2011. DOI:10.1097/QAD.0b013e32834fa13d ISSN 0269-9370 Q 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 497