Use of hormonal contraceptives and risk of HIV-1 transmission: a prospective cohort study

Abstract

Summary Background Hormonal contraceptives are used widely but their effects on HIV-1 risk are unclear. Methods We followed 3790 heterosexual HIV-1 serodiscordant couples from seven African countries participating in two longitudinal HIV-1 incidence studies. Among hormonal contraceptive users (including injectable and oral contraceptive users) and nonusers, we compared rates of HIV-1 acquisition in women and HIV-1 transmission from women to men. Findings Among 1314 couples in which the HIV-1 seronegative partner was female, HIV-1 acquisition rates were 6.61 and 3.78 per 100 person-years among hormonal contraceptive users and nonusers (adjusted hazard ratio [AHR]=1.98, 95% confidence interval [CI] 1.06–3.68, p=0.03). Among 2476 couples in which the HIV-1 seronegative partner was male, HIV-1 transmission rates from women to men were 2.61 and 1.51 per 100 person-years in those whose partners currently used versus did not use hormonal contraception (AHR=1.97, 95% CI 1.12–3.45, p=0.02). In subgroup analysis, injectable contraceptive users had increased risk for acquiring and transmitting HIV-1 to their partner and HIV-1 seropositive women using injectable contraception had higher genital HIV-1 RNA concentrations, suggesting a mechanism for increased transmission risk. Oral contraceptives were used too infrequently to draw definitive conclusions about HIV-1 risk. Interpretation Women should be counseled about potentially increased risk of HIV-1 acquisition and transmission with hormonal contraception, particularly injectable methods, and about the importance of dual protection with condoms to decrease HIV-1 risk. Non-hormonal or lower-dose hormonal contraceptive methods should be considered for women with or at-risk for HIV-1. Funding National Institutes of Health (R03 HD068143, R01 AI083034, P30 AI027757, and T32 AI007140) and the Bill and Melinda Gates Foundation (26469 and 41185).

Population-level impact of hormonal contraception on incidence of HIV infection and pregnancy in women in Durban, South Africa

“…[12][13][14][15][16][17] These findings were supported by a subsequent study by Heffron et al that provided new evidence suggesting an increased risk of contracting and transmitting HIV-1 infection associated with the use of hormonal contraceptives, particularly injectables. 18 Durban data from the MDP301 trial confirmed this. 19 Morrison et al combined the multisite data from the Carraguard® trial, including the Durban site data, and showed a moderately increased risk of HIV-1 seroconversion with the use of the injectable progestin depo-medroxyprogesterone acetate, but no effect with other types of hormonal contraceptives.…”

“…28 Heffron et al reported a significant association between use of hormonal contraceptives and HIV-1 seroconversion with a reasonably large effect size (adjusted HR: 1.98; 95% CI: 1.06-3.68). 18 The study reported that almost 15% of women were using hormonal contraceptives at enrolment and 21% at follow-up. Given this data, determining the population-level impact is critical.…”

“…Heffron et al also reported pregnancy rates of 5.2% and 16.0% among women who did and who did not report using hormonal contraceptives, respectively. 18 Since the adjusted hazard ratio was not presented, the percentage of pregnancies attributed to the use of other types of contraceptives in adjusted analyses could not be estimated. However, a large absolute difference between rates of HIV-1 seroconversion and pregnancy rates may indicate that hormonal injectable contraceptives have a large population-level impact in terms of preventing pregnancies in the target population.…”

“…[12][13][14][29][30][31] Conflicting study outcomes have triggered doubts regarding the role of injectable contraceptives and their use in developing countries. [12][13][14][15][16][17][18] It is critical to determine to what degree hormonal contraceptives increase the risk of HIV-1 infection. Although studies designed to address this question may be complex and difficult to implement, such difficulty must be weighed against their potential impact on HIV-1 acquisition.…”

“…Resultados El riesgo de seroconversión del VIH-1 fue superior en las mujeres que declararon utilizar anticonceptivos hormonales en el momento de la inscripción en el ensayo (índice de riesgos ajustado: 1,24; IC del 95%: 0,97-1,58) que en las mujeres que declararon utilizar otros tipos de anticonceptivos. Entre la población, el uso de anticonceptivos hormonales (píldoras o inyectables) en el punto de partida y durante el seguimiento del estudio representó aproximadamente el 20% (IC del 95%: [16][17][18][19][20][21][22] de las seroconversiones del VIH-1. No obstante, el riesgo parcial atribuible a la población indicó un impacto relativo del 12% (IC del 95%: 9.0-15.7).…”