Articles tagged as "Hormonal contraception and HIV risk"

No evidence of an increased risk of female-male HIV transmission with hormonal contraception in Zambia

Hormonal contraceptive use among HIV-positive women and HIV transmission risk to male partners, Zambia, 1994-2012.

Wall KM, Kilembe W, Vwalika B, Ravindhran P, Khu NH, Brill I, Chomba E, Johnson BA, Haddad LB, Tichacek A, Allen S. J Infect Dis. 2016 Oct 1;214(7):1063-71. doi: 10.1093/infdis/jiw322. Epub 2016 Jul 26.

Background: Evidence on the association between female-to-male human immunodeficiency virus (HIV) transmission risk and hormonal contraception is sparse and conflicting.

Methods: Heterosexual HIV-discordant couples from Lusaka, Zambia, were followed longitudinally at 3 month-intervals from 1994 to 2012. The impact of hormonal contraception on time to HIV transmission from HIV-positive women to their HIV-negative male partners (M-F+) was evaluated.

Results: Among 1601 M-F+ couples, 171 genetically linked HIV transmissions occurred in men over 3216 couple-years (5.3 transmissions/100 couple-years; 95% confidence interval [CI], 4.5-6.2). In multivariable Cox models, neither injectable (adjusted hazard ratio [aHR], 0.6; 95% CI, .4-1.2), oral contraceptive pill (aHR, 0.8; 95% CI, .3-2.1), nor implant (aHR, 0.8; 95% CI, .5-1.4) use was associated with HIV transmission, relative to nonhormonal methods, after controlling for the man's age at baseline and time-varying measures of pregnancy, self-reported unprotected sex with the study partner, sperm present on a vaginal swab wet mount, genital inflammation of either partner, genital ulceration of the man, and first follow-up interval. Sensitivity analyses, including marginal structural modeling and controlling for viral load and fertility intentions available in a subset of couples, led to similar conclusions.

Conclusions: Our findings suggest null associations between hormonal contraception and risk of female-to-male HIV transmission. We support efforts to increase the contraceptive method mix for all women, regardless of HIV serostatus, along with reinforced condom counseling for HIV-serodiscordant couples.

Abstract  Full-text [free] access 

Editor’s notes: Evidence suggests that certain injectable hormonal contraceptives (particularly depot medroxyprogesterone acetate [DMPA]) may increase HIV risk in women. However, few studies have assessed whether hormonal contraception increases the risk of female-male transmission. This paper presents results from an 18-year prospective follow-up study in Zambia. In the study, the investigators were able to analyse biologically linked results of serodiscordant couples and multiple methods of contraception. Their findings suggest no evidence of an increased risk of HIV transmission from women living with HIV to their male partners. In fact, couples with a linked transmission were less likely to use injectable contraceptives than women using non-hormonal methods (not statistically significant). This is encouraging; however, there are potential confounding factors in this study, such as high circumcision rates among men and low viral loads among women. The results also conflict with two earlier studies that found an increased risk of female-male transmission associated with hormonal contraception. More research is therefore necessary to provide evidence on this topic and enable recommendations on the use of hormonal contraception among serodiscordant couples.

  • share

Updated evidence that DMPA increases HIV risk among women

Update on hormonal contraceptive methods and risk of HIV acquisition in women: a systematic review of epidemiological evidence, 2016.

Polis CB, Curtis KM, Hannaford PC, Phillips SJ, Chipato T, Kiarie JN, Westreich DJ, Steyn PS. AIDS. 2016 Aug 5. [Epub ahead of print]

Objective and design: Some studies suggest that specific hormonal contraceptive (HC) methods (particularly depot medroxyprogesterone acetate [DMPA]) may increase women's HIV acquisition risk. We updated a systematic review to incorporate recent epidemiological data.

Methods: We searched for articles published between 1/15/2014-1/15/2016, and hand-searched reference lists. We identified longitudinal studies comparing users of a specific HC method against either (1) non-users of HC, or (2) users of another specific HC method. We added newly identified studies to those in the previous review, assessed study quality, created forest plots to display results, and conducted a meta-analysis for data on DMPA versus no HC.

Results: We identified ten new reports: five were considered "unlikely to inform the primary question". We focus on the other five reports, along with 9 from the previous review, considered "informative but with important limitations". The preponderance of data for oral contraceptive pills, injectable norethisterone enanthate (NET-EN), and levonorgestrel implants do not suggest an association with HIV acquisition, though data for implants are limited. The new, higher-quality studies on DMPA (or non-disaggregated injectables), which had mixed results in terms of statistical significance, had hazard ratios (HR) between 1.2 and 1.7, consistent with our meta-analytic estimate for all higher-quality studies of HR 1.4.

Conclusions: While confounding in these observational data cannot be excluded, new information increases concerns about DMPA and HIV acquisition risk in women. If the association is causal, the magnitude of effect is likely ≤HR 1.5. Data for other hormonal contraceptive methods, including NET-EN, are largely reassuring.

Abstract access

Editor’s notes: For several years there has been debate about whether the risk of HIV acquisition in women may be increased by the use of hormonal contraception. A systematic review published in 2014 included a meta-analysis of data from 22 studies, and this paper adds 10 new studies to the analysis. While these new papers carried some of the previous review’s limitations which cannot be ignored, the new data also lends further strength to the evidence and renewed analysis. The authors found some encouraging results which suggest that there is no significant increased risk of HIV with the use of oral contraceptives and the NET-EN injectable. However, this analysis does suggest that there is an increased risk of 1.4-1.5 of HIV with the use of DMPA. This is particularly concerning given the widespread use of this product throughout the world, and especially in areas where high rates of new HIV infections continue to persist, such as sub-Saharan Africa. Studies continue to explore this association of risk, and will hopefully produce evidence in the near future to definitively provide guidance as to how clinicians should direct the use of DMPA in women at risk of HIV. 

Africa, Northern America
  • share

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, 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

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.

South Africa
  • share

Further evidence of an association with the injectable contraceptive, depot-medroxyprogesterone acetate with risk of HIV

Hormonal contraception and the risk of HIV acquisition: an individual participant data meta-analysis.

Morrison CS, Chen PL, Kwok C, Baeten JM, Brown J, Crook AM, Van Damme L, Delany-Moretlwe S, Francis SC, Friedland BA, Hayes RJ, Heffron R, Kapiga S, Karim QA, Karpoff S, Kaul R, McClelland RS, McCormack S, McGrath N, Myer L, Rees H, van der Straten A, Watson-Jones D, van de Wijgert JH, Stalter R, Low N. PLoS Med. 2015 Jan 22;12(1):e1001778. doi: 10.1371/journal.pmed.1001778. eCollection 2015.

Background: Observational studies of a putative association between hormonal contraception (HC) and HIV acquisition have produced conflicting results. We conducted an individual participant data (IPD) meta-analysis of studies from sub-Saharan Africa to compare the incidence of HIV infection in women using combined oral contraceptives (COCs) or the injectable progestins depot-medroxyprogesterone acetate (DMPA) or norethisterone enanthate (NET-EN) with women not using HC.

Methods and findings: Eligible studies measured HC exposure and incident HIV infection prospectively using standardized measures, enrolled women aged 15-49 y, recorded ≥15 incident HIV infections, and measured prespecified covariates. Our primary analysis estimated the adjusted hazard ratio (aHR) using two-stage random effects meta-analysis, controlling for region, marital status, age, number of sex partners, and condom use. We included 18 studies, including 37 124 women (43 613 woman-years) and 1830 incident HIV infections. Relative to no HC use, the aHR for HIV acquisition was 1.50 (95% CI 1.24-1.83) for DMPA use, 1.24 (95% CI 0.84-1.82) for NET-EN use, and 1.03 (95% CI 0.88-1.20) for COC use. Between-study heterogeneity was mild (I2 < 50%). DMPA use was associated with increased HIV acquisition compared with COC use (aHR 1.43, 95% CI 1.23-1.67) and NET-EN use (aHR 1.32, 95% CI 1.08-1.61). Effect estimates were attenuated for studies at lower risk of methodological bias (compared with no HC use, aHR for DMPA use 1.22, 95% CI 0.99-1.50; for NET-EN use 0.67, 95% CI 0.47-0.96; and for COC use 0.91, 95% CI 0.73-1.41) compared to those at higher risk of bias (pinteraction = 0.003). Neither age nor herpes simplex virus type 2 infection status modified the HC-HIV relationship.

Conclusions: This IPD meta-analysis found no evidence that COC or NET-EN use increases women's risk of HIV but adds to the evidence that DMPA may increase HIV risk, underscoring the need for additional safe and effective contraceptive options for women at high HIV risk. A randomized controlled trial would provide more definitive evidence about the effects of hormonal contraception, particularly DMPA, on HIV risk.

Abstract  Full-text [free] access

Editor’s notes: As seen in the paper published this month by Ralph et al, observational studies have reported that hormonal contraception, in particular injectable progestins depot-medroxyprogesterone acetate (DMPA), may increase risk of HIV infection. This individual patient data meta-analysis adds further to the evidence. A major strength of the study is the large sample size. It provides sufficient power to examine associations between specific contraceptives and HIV risk and to investigate effect modification in pre-specified sub-group analyses. Furthermore, using individual-level data allowed a consistent approach to coding and adjustment for confounding. If the association is real, this has important implications for sexual and reproductive health in areas of sub-Saharan Africa where the incidence of HIV acquisition and unintended pregnancy is high.



Hormonal contraceptive use and women's risk of HIV acquisition: a meta-analysis of observational studies.

Ralph LJ, McCoy SI, Shiu K, Padian NS. Lancet Infect Dis. 2015 Jan 8. pii: S1473-3099(14)71052-7. doi: 10.1016/S1473-3099(14)71052-7. [Epub ahead of print]

Background: The evidence from epidemiological research into whether use of hormonal contraception increases women's risk of HIV acquisition is inconsistent. We did a robust meta-analysis of existing data to provide summary estimates by hormonal contraceptive method which can be used to inform contraceptive guidelines, models, and future studies.

Methods: We updated a recent systematic review to identify and describe studies that met inclusion criteria. To ensure inclusion of more recent research, we searched PubMed for articles published after December, 2011, using the terms "hormonal contraception", "HIV/acquisition", "injectables", "progestin", and "oral contraceptive pills". We assessed statistical heterogeneity for these studies, and, when appropriate, combined point estimates by hormonal contraception formulation using random-effects models. We assessed publication bias and investigated heterogeneity through subgroup and stratified analyses according to study population and design features.

Findings: We identified 26 studies, 12 of which met inclusion criteria. There was evidence of an increase in HIV risk in the ten studies of depot medroxyprogesterone acetate (pooled hazard ratio [HR] 1.40, 95% CI 1.16-1.69). This risk was lower in the eight studies done in women in the general population (pooled HR 1.31, 95% CI 1.10-1.57). There was substantial between-study heterogeneity in secondary analyses of trials (n=7, I2 51.1%, 95% CI 0-79.3). Although individual study estimates suggested an increased risk, substantial heterogeneity between two studies done in women at high risk of HIV infection (I2 54%, 0-88.7) precluded pooling estimates. There was no evidence of an increased HIV risk in ten studies of oral contraceptive pills (pooled HR 1.00, 0.86-1.16) or five studies of norethisterone enanthate (pooled HR 1.10, 0.88-1.37).

Interpretation: Our findings show a moderate increased risk of HIV acquisition for all women using depot medroxyprogesterone acetate, with a smaller increase in risk for women in the general population. Whether the risks of HIV observed in our study would merit complete withdrawal of depot medroxyprogesterone acetate needs to be balanced against the known benefits of a highly effective contraceptive.

Abstract access

Editor’s notes: This meta-analysis has similar findings to the individual patient data (IPD) meta-analysis by Morrison et al, also published this month. The study finds that depot medroxyprogesterone (DMPA) is associated with a moderate increase in HIV risk, and little evidence of a risk associated with combined oral contraceptives or norethisterone enanthate (NET-EN). The policy implications of this finding are unclear. As with the IPD analysis, this meta-analysis is based on observational studies and does not provide conclusive evidence that DMPA causes the increased risk of HIV. However, it does provide refined estimates for modelling studies to assess the implications of possible withdrawal of DMPA on maternal and HIV-associated mortality, so that context-specific contraceptive policies can be considered.

  • share