DMPA contraception users more likely than NET-EN users to acquire HIV in South Africa

Risk of HIV-1 acquisition among women who use different types of injectable progestin contraception in South Africa: a prospective cohort study.

Noguchi LM, Richardson BA, Baeten JM, Hillier SL, Balkus JE, Chirenje ZM, Bunge K, Ramjee G, Nair G, Palanee-Phillips T, Selepe P, van der Straten A, Parikh UM, Gomez K, Piper JM, Watts DH, Marrazzo JM. Lancet HIV. 2015 Jul 1;2(7):e279-e287.

Background: Several observational studies have reported that HIV-1 acquisition seems to be higher in women who use depot medroxyprogesterone acetate (DMPA) than in those who do not use hormonal contraception. We aimed to assess whether two injectable progestin-only contraceptives, DMPA and norethisterone enanthate (NET-EN), confer different risks of HIV-1 acquisition.

Methods: We included data from South African women who used injectable contraception while participating in the VOICE study, a multisite, randomised, placebo-controlled trial that investigated the safety and efficacy of three formulations of tenofovir for prevention of HIV-1 infection in women between Sept 9, 2009, and Aug 13, 2012. Women were assessed monthly for contraceptive use and incident infection. We estimated the difference in incident HIV-1 infection between DMPA and NET-EN users by Cox proportional hazards regression analyses in this prospective cohort. The VOICE trial is registered with ClinicalTrials.gov, NCT00705679.

Findings: 3141 South African women using injectable contraception were included in the present analysis: 1788 (56.9%) solely used DMPA, 1097 (34.9%) solely used NET-EN, and 256 (8.2%) used both injectable types at different times during follow-up. During 2733.7 person-years of follow-up, 207 incident HIV-1 infections occurred (incidence 7.57 per 100 person-years, 95% CI 6.61-8.68). Risk of HIV-1 acquisition was higher among DMPA users (incidence 8.62 per 100 person-years, 95% CI 7.35-10.11) than among NET-EN users (5.67 per 100 person-years, 4.35-7.38; hazard ratio 1.53, 95% CI 1.12-2.08; p=0.007). This association persisted when adjusted for potential confounding variables (adjusted hazard ratio [aHR] 1.41, 95% CI 1.06-1.89; p=0.02). Among women seropositive for herpes simplex virus type 2 (HSV-2) at enrolment, the aHR was 2.02 (95% CI 1.26-3.24) compared with 1.09 (0.78-1.52) for HSV-2-seronegative women (pinteraction=0.07).

Interpretation: Although moderate associations in observational analyses should be interpreted with caution, these findings suggest that NET-EN might be an alternative injectable drug with a lower HIV risk than DMPA in high HIV-1 incidence settings where NET-EN is available.

Abstract access [1]

Editor’s notes: In eastern and southern Africa, injectable methods are the most popular contraceptives. But evidence that the injectable progestin depot medroxyprogesterone acetate (DMPA) is associated with an increased risk of HIV-1 acquisition means that alternative injectable contraceptive methods are necessary. This large prospective study used data from the VOICE HIV prevention trial, analysing data from South Africa on 3141 women who had used one of two progestin methods for contraception. HIV incidence was high in the population (7.57/100 person-years overall), and participants who used DMPA were 40% more likely to become HIV positive than women who used norethisterone enanthate (NET-EN) after adjustment for demographic and behavioural confounding variables. Strengths of this study include the comparability across women using progestin methods, and its frequent follow up visits to assess HIV status, contraception use, sexual behaviour and the presence of reproductive tract infections. The results suggest NET-EN might be an alternative injectable contraceptive with a lower risk for HIV-1 acquisition than DMPA.

Africa [8]
South Africa [9]
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