Empowering women and couples with the tools necessary to prevent unintended pregnancy and avoid sexually transmitted infections including HIV is critically important for individual and public health. Hormonal contraceptive methods are highly effective for prevention of unintended pregnancy and associated sequelae. However, some epidemiological studies suggest an association between use of specific hormonal contraceptive methods [particularly depot medroxyprogesterone acetate (DMPA)] and an increased risk of HIV acquisition in women; other studies have not reported this association . This question is critically important for women's health, particularly in sub-Saharan Africa, where high rates of HIV coincide with high use of injectable contraception . Many regions with high HIV prevalence also have high rates of unmet need for contraception, unintended pregnancy, and maternal mortality and morbidity, underlying the imperative for access to effective contraception [3,4].
Several biologically plausible mechanisms have been postulated to explain how various hormonal contraceptive methods could increase women's risk of HIV acquisition, including possible disruption of epithelial barriers, alterations in immune cell populations, or soluble inflammatory responses [5–8]. The effect of hormonal contraception on cervical immunity is influenced by the genital tract microenvironment and presence of infections . Interpretation of current data on biologic and immunologic impacts from hormonal contraceptive use is hampered by studies that fail to account for different hormones, diverse dosages, and hormonal contraceptive delivery routes . Women using particular hormonal contraceptive methods may also have other characteristics (e.g. different patterns of condom use), which could impact HIV acquisition risk.
A previous systematic review of epidemiological evidence assessed all relevant evidence published prior to 15 January 2014 . The review was conducted independently of the WHO guidance development process and served as an input into WHO deliberations related to updating the medical eligibility criteria for contraceptive use (refer to Appendix A, http://links.lww.com/QAD/A969 for current WHO guidance for hormonal contraceptive use among women at high risk of HIV) . Given the public health importance of this topic, we updated our previous systematic review to incorporate newly published, pertinent epidemiological evidence.
We conducted this systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines .
We included published primary research reports on women who were HIV-negative at baseline in longitudinal studies (observational studies or randomized trials, or meta-analyses containing data not otherwise captured in our search strategy) that measured incident, laboratory-confirmed HIV infection among women who used a specific method of hormonal contraception [injectables, oral contraceptives, implants, patches, rings, or levonorgestrel intrauterine devices (LNG-IUDs)] compared with incident HIV infections among women using a nonhormonal contraceptive method (e.g. condoms, nonhormonal IUD, sterilization, withdrawal, etc.) or no contraceptive method (henceforth, ‘hormonal contraceptive versus non-use of hormonal contraception’ comparisons). Some studies compared hormonal contraceptive users against a heterogeneous group including other hormonal contraceptive users, nonhormonal method users, and nonusers of contraception. We identified and included such studies, but considered the composition of the comparison group when assessing study quality.
We also included studies comparing incident HIV infection among HIV-negative women using a specific method of hormonal contraception against HIV-negative women using another specific method of hormonal contraception (henceforth, ‘head-to-head’ analyses) in which the comparison group did not contain nonhormonal method users or nonusers of contraception.
We excluded studies that did not report a risk estimate for the relationship between hormonal contraceptive use and HIV acquisition, cross-sectional studies, studies assessing only emergency contraception, conference abstracts, or other unpublished reports.
We retained all articles included in the previous systematic review, unless superseded by a new published analysis based upon the same data. We searched PubMed and Embase (Appendix B, http://links.lww.com/QAD/A969) for articles published in any language between 15 January 2014 and 15 January 2016, inclusive. We hand-searched reference lists of included studies. C.B.P. conducted the literature search and C.B.P., K.M.C., and P.C.H. screened titles, abstracts, and full-text manuscripts to determine inclusion using Covidence software .
Data extraction and quality assessment
We applied a study quality assessment framework used in our 2014 systematic review, with slight modifications for clarity . Briefly, studies that did not include adjustment for condom use or which had unclear measurement of exposure to hormonal contraception (refer to Appendix C, http://links.lww.com/QAD/A969 for a full explanation of the quality assessment criteria) were considered ‘unlikely to inform the primary question’. For comprehensiveness, we included all studies that met our inclusion criteria, regardless of quality. However, we focused on studies with neither of the two quality concerns noted above; we considered these studies ‘informative but with important limitations’ (IBWILs) to acknowledge that all studies to date are vulnerable to residual or uncontrolled confounding. All authors participated in confirming the study quality assessment framework and in rating the quality of each study. We adapted previously used abstraction forms that were pilot tested by all coauthors. All coauthors abstracted data from each newly included study that was considered as IBWIL. We contacted study investigators if clarifications were needed.
We created forest plots using Microsoft Excel 2013 (Microsoft, Redmond, Washington, USA) to summarize point estimates for a given contraceptive method [i.e. oral contraceptives, injectables (nonspecified, DMPA, and norethisterone enanthate (NET-EN)), or implants]. We focus on graphics summarizing only studies considered IBWIL, but graphs depicting all studies regardless of quality are provided in Appendix D, http://links.lww.com/QAD/A969.
Most studies estimated hazards ratios using Cox proportional hazards models; some also included estimates from a marginal structural model (MSM) (for additional discussion, refer to [1,13]). A few estimated only incidence rate ratios (IRRs) (Tables 1 and 2). For clarity of presentation, we display the IRR or Cox hazards ratio, unless the MSM model generated qualitatively different estimates, in which case both Cox and MSM estimates are shown.
As in 2014, we requested disaggregated estimates from authors of new studies classified as IBWIL and which included women from South Africa (where use of both DMPA and NET-EN is common) but which did not report separate estimates for each. Disaggregated estimates have reduced statistical power but greater epidemiological and clinical value, given the potential for different biological effects by contraceptive type or formulation.
Given concerns specific to DMPA, we performed a statistical meta-analysis for the effect of DMPA versus non-use of hormonal contraception on HIV acquisition (studies that did not disaggregate injectables were not included). For maximum comparability, we included the most fully adjusted Cox hazards ratio estimates from each study, except one that reported an adjusted IRR (IRRs can be interpreted similarly to hazards ratios under certain conditions ). We log-transformed reported adjusted point estimates and 95% confidence intervals (95% CIs) to calculate standard errors using a random effects model . We assessed statistical heterogeneity using the I2 statistic . Analyses were performed using Stata (Version 13.1, College Station, Texas, USA).
Description of included studies
Twenty-two studies were included in our previous review . For this review, we screened 312 new references, assessed 14 full-text reports, and excluded four: two did not report on the association of interest [17,18] and two meta-analyses contained published data already captured by our search strategy (including them would have resulted in double-counting of data, instead they are mentioned in our discussion) (Fig. 1) [19,20].
We included 10 new reports [21–30]; one  superseded a previously included study . A large, individual participant data (IPD) meta-analysis  used raw data from 18 datasets, including seven not previously utilized to investigate the association of interest [17,32–37]. To incorporate the previously unpublished information (while avoiding double-counting from previously published studies), we requested a subanalysis restricted to data from these seven studies in a hormonal contraceptive versus non-use of hormonal contraception comparison . The IPD meta-analysis also included a head-to-head comparison that none of our included component studies had assessed; here we used results from the original article .
Table 1 describes 10 newly included studies; information on previously included studies is available elsewhere . A total of 31 studies (comprising 34 reports) were included [21–30,39–62]. Thirty assessed hormonal contraceptive versus non-use of hormonal contraception comparisons [21–29,39–62] and two assessed head-to-head comparisons [26,30].
Among 30 studies with hormonal contraceptive versus non-use of hormonal contraception comparisons, 24 included estimates specific to (or largely composed of) oral contraceptives [21–24,26,27,29,39,41–46,49–53,55–59,61,62]. Twenty-four included estimates specific to (or largely composed of) injectables [21,24–29,39–48,50–53,55,56,58,60,62] and three included implant-specific estimates [27,39,50,54]. All studies assessing DMPA assessed intramuscular DMPA, rather than the lower dose, subcutaneous formulation. No study assessed contraceptive patches, rings, combined injectables, or LNG-IUDs. Among two head-to-head studies, two compared DMPA versus NET-EN [26,30] and one compared DMPA versus combined oral contraceptives (COCs) and NET-EN versus COCs .
Hormonal contraceptive versus non-use of hormonal contraception studies considered informative but with important limitations
Of 30 hormonal contraceptive versus non-use of hormonal contraception, we rated 12 as IBWIL [21,26,27,29,39,42,43,47,51–53,55,56,58], including four newly identified studies [21,26,27,29]. Table 2 provides details on new IBWIL studies; information on previously included IBWIL studies is available elsewhere . The four new studies included a large IPD meta-analysis that assessed oral contraceptives, DMPA, and NET-EN across a range of datasets , an analysis from an 18-year cohort study of Zambian serodiscordant couples to assess oral contraceptives, DMPA, and implants , and two analyses from large microbicide trials, one assessing unspecified injectables  and the other assessing oral contraceptives, DMPA, and NET-EN . Below, we summarize results from all 12 hormonal contraceptive versus non-use of hormonal contraception studies considered IBWIL. Readers should consult the relevant tables and figures for additional detail (such as 95% CIs); descriptions below provide a succinct synthesis of the overall evidence base. We discuss studies according to whether results were significant at P less than 0.05, but acknowledge that, considered alone, P values are an imperfect indicator of significance .
Neither of two IBWIL studies assessing levonorgestrel-based implants (Norplant or Jadelle) [27,39,54] suggested a statistically significant increased risk of HIV. Point estimates ranged from adjusted hazards ratio (adjHR) 0.96 to 1.60; 95% CIs were wide.
Of 11 IBWIL studies assessing oral contraceptives [21,26,27,29,38,39,42,51–53,55,56,58], one reported a marginally significant increase in risk (adjHR: 1.46, P = 0.05); 10 reported nonsignificant estimates ranging from adjusted incidence rate ratios (adjIRR) 0.66 to adjHR 1.80 (Fig. 2). One study disaggregated COCs and progestin-only pills (POPs); point estimates were similar and nonsignificant (adjHR: 0.86 and 0.98, respectively) .
Of 12 IBWIL studies assessing injectables (DMPA, NET-EN, or a mix of both) [21,26,27,29,38,39,42,47,51–53,55,56,58], nine provided DMPA-specific estimates and three provided estimates for unspecified injectables. Five studies reported a statistically significant increase in risk with either unspecified injectables  or DMPA [21,26,38,39,52,53], although the point estimate in one was not statistically significant in a Cox proportional hazards model  (Figs. 3 and 4). Point estimates from Cox models from these five studies ranged from adjHR 1.45 to 2.04 (Figs. 3 and 4) [21,26,38,39,42,52,53]; the largest estimate under an MSM model was 2.19 . Among seven studies reporting nonstatistically significant results, point estimates ranged from adjIRR 0.46 to adjHR 1.34 (both DMPA-specific) [27,29,47,51,55,56,58]. None of six studies assessing NET-EN reported statistically significant increases in HIV risk: point estimates ranged from adjHR 0.87 to adjIRR 1.76 (Fig. 5) [21,26,38,47,51,55,56].
Head-to-head studies considered informative but with important limitations
No head-to-head comparison studies were available in the previous review . Both newly included head-to-head studies were considered IBWIL (Tables 1 and 2) [26,30]. Both reported a statistically significant increased risk of HIV for DMPA use (adjHR: 1.32 and 1.41) versus NET-EN use [26,30]. The IPD meta-analysis also compared each injectable against COCs, reporting significantly increased risk for DMPA versus COCs (adjHR: 1.43, 95% CI: 1.23–1.67) and a borderline nonsignificant increased risk for NET-EN versus COCs: adjHR 1.30 (0.99–1.71) (Fig. 6) .
Ten estimates, from nine published studies with DMPA-specific estimates versus non-use of hormonal contraception [21,27,39,42,47,51,53,55,56] and a subanalysis of previously unpublished information from an IPD meta-analysis , were included in our meta-analysis of the effect of DMPA on HIV acquisition (Appendix D, Fig. 5, http://links.lww.com/QAD/A969). The overall effect estimate was 1.40 (95% CI: 1.23–1.59) with an I2 of 0%, indicating minimal quantitative heterogeneity.
One study reported increased HIV risk with DMPA and oral contraceptives in younger (18–24 years) but not older women ; eight studies reported no effect modification by age [21,27,29,39,42,47,51,56]; most studies reported no effect modification by herpes simplex virus type 2 (HSV-2) status [21,29,39,42,51], whereas two reported effect modification in opposite directions [One observed higher HIV risk with DMPA in HSV-2 seronegative women (Morrison et al.) and the other observed higher HIV risk with DMPA (versus NET-EN) in HSV-2 seropositive women (Noguchi et al.).]. Two studies reported no effect of modification by study site [21,30], one reported greater risk for oral contraceptives and DMPA in a Ugandan site versus a Zimbabwean site . A study in serodiscordant couples reported no effect modification for genital ulceration, inflammation, viral load of HIV-positive partner at baseline, or fertility intentions . Another study reported no effect modification by reported condom use at baseline, participant behavioral risk, or prevalent chlamydia or gonorrhea .
Within the IPD meta-analysis, assessment for effect modification was conducted with information from all 18 studies (some of which were also included in our review). No evidence of interaction was reported with any method for age (15–24 versus >25 years), HSV-2 status at baseline, or HIV incidence in population (low versus high) . Increased HIV risk was observed for COC use in East Africa (adjHR: 1.58, 95% CI: 1.19–2.09) but not South Africa or Southern Africa, and for DMPA use in east and South Africa (adjHR: 2.09, 95% CI: 1.68–2.80; adjHR: 1.30, 95% CI: 1.11–1.53), but not Southern Africa. Populations that reported engaging in transactional sex work had an increased HIV risk with COCs (adjHR: 1.51, 95% CI: 1.09–2.10) unlike populations without transactional sex work. Finally, smaller point estimates were observed among studies deemed by the investigators as at lower risk of methodological bias: adjHR for DMPA: 1.22 (95% CI: 0.99–1.50) and adjHR for NET-EN: 0.67 (95% CI: 0.47–0.96). Table 3 details how the IPD meta-analysis investigators defined lower risk of bias in comparison with our quality criteria.
Interpretation of overall results
As in our 2014 review, current data do not suggest an increased risk of HIV acquisition among women using oral contraceptives . Extremely limited data do not suggest a statistically significant increased risk of HIV acquisition among users of levonorgestrel implants; no data are available regarding etonogestrel implants. In 2014, one of five studies that was considered IBWIL suggested an increased risk of HIV acquisition with NET-EN injectables . In this updated review, that study was replaced by a larger, more sophisticated analysis of the same dataset , and increased HIV risk was no longer observed. Thus, currently available data for injectable NET-EN use do not suggest an association with HIV acquisition in women.
Although concerns around confounding in observational data remain relevant, newly available evidence regarding injectable DMPA use increases concern about a potential causal association with HIV acquisition. Twelve studies considered IBWIL assessed DMPA or nondisaggregated injectables compared with non-use of hormonal contraception; four or five (depending on the statistical model considered) reported statistically significant increased risks of HIV acquisition, ranging from adjHR 1.45 to 2.04 in Cox models (or 2.19 in MSM models). Among four newly included studies, two reported statistically significant increased risk (adjHR: 1.45 and 1.69), including one very large study  and a subanalysis of a large IPD meta-analysis . A smaller study among serodiscordant couples  reported a nonsignificant estimate of adjHR 1.34, and data from a microbicide trial also had a nonsignificant estimate of adjHR 1.17 but did not disaggregate between injectables . Head-to-head comparisons were newly available and may be less confounded by unmeasured or residual behavioral differences than comparisons from hormonal contraceptive versus non-use of hormonal contraception studies, particularly if groups compared in head-to-head studies use different types of the same delivery method (i.e., injectable DMPA versus injectable NET-EN) . A head-to-head analysis of VOICE data reported a 41% increased risk of HIV acquisition in DMPA versus NET-EN users . In the IPD meta-analysis , DMPA use was associated with a significantly increased risk of HIV acquisition of 30–40% when compared with either NET-EN or COC use. Comparing NET-EN against COC users suggested higher risk with NET-EN, though this was not statistically significant at P less than 0.05 (P = 0.055). Although residual confounding cannot be ruled out in any observational study, several recently published studies suggesting an increased risk of HIV acquisition among DMPA users had few limitations apart from being observational (Table 2).
Recent analyses contradict the hypothesis that differential over-reporting of condom use by hormonal contraceptive users explains observed associations between hormonal contraceptive use and HIV infection in some studies . However, the possibility remains that certain confounders are specific to DMPA users. In South Africa (where both DMPA and NET-EN injectables are used), studies suggest that women perceive DMPA and NET-EN differently, and providers may preferentially prescribe different injectable types to specific subpopulations, which could result in confounding specific to injectable type [30,65,66]. Although beyond the scope of this review, emerging evidence related to DMPA and HSV-2 acquisition must also be considered [67,68].
Taken together, the new evidence points toward heightened concerns that the association between DMPA use and HIV acquisition may not be fully explained by confounding or other methodological problems. In contrast, additional reassuring evidence of no significant association for other hormonal contraceptive methods (oral contraceptives, NET-EN, and implants) is newly available. If the association between DMPA and HIV acquisition risk is causal, meta-analyses, including our own, suggest a likely increase in risk of hazards ratio 1.5 or less.
The quality of epidemiological evidence on this issue has improved over time. Several newly published studies used recent analytic recommendations  or other innovative analytic techniques. For example, Crook et al. conducted a particularly thorough exploration of statistical methodology and incorporated multiple sensitivity analyses to assess the robustness of their findings, Morrison et al. contributed substantial new data in a carefully conducted IPD meta-analysis, and Noguchi et al. examined an alternative comparison group (NET-EN users).
The methodological contribution of three newly published meta-analyses varied. In addition to the IPD meta-analysis included in our review , two meta-analyses [19,20] utilized data already included as primary studies in our systematic reviews (thus, adding no information beyond that already included in this review). Although all three meta-analyses reported summary estimates for DMPA similar to our own (hazards ratio 1.4–1.5), one of the excluded meta-analyses contained no assessment of study quality and included several studies with serious methodological limitations , which raises particular concern in the context of meta-analysis of observational data (Table 3) . Both excluded meta-analyses [19,20] double-counted  data by inclusion of both Wand and Ramjee  and Crook et al.. We generated a meta-analytic estimate for DMPA, but recommend that such results be interpreted with caution, given the potential for spurious precision in meta-analyses of observational data . The I2 value for our meta-analysis suggested minimal statistical heterogeneity, but qualitative differences between study populations and methods remain an important consideration . That said, estimates from all four meta-analyses are similar, despite inclusion of slightly different component studies .
Previous reviews have addressed key methodological considerations about this body of literature, including potential for confounding, frequency, and accuracy of variable measurement, considerations related to ‘direct’ and ‘total’ effects, potential for publication bias, and limitations of individual studies, such as failure of some studies to disaggregate by specific hormonal content or formulation (e.g., most studies assessing oral contraceptives failed to disaggregate estimates by COCs or POPs) [1,72]. Our study quality framework is necessarily subjective, and we encourage continued discussion on how best to evaluate study quality in this body of evidence.
There remain no data on use of contraceptive patches, rings, or hormonal IUDs and HIV acquisition in women. For implants, very limited data pertaining to levonorgestrel implants do not suggest increased risk, but more information is needed. In comparison, a larger amount of data are available for oral contraceptives and are generally reassuring. A growing number of studies have assessed injectable NET-EN, and although still limited, data are generally reassuring. For injectable DMPA, although some new, high-quality studies do not report a statistically significant increased risk of HIV acquisition, other new data, including studies directly comparing DMPA and NET-EN, tend to strengthen concerns about DMPA. If the association between DMPA and HIV acquisition risk is causal, data suggest a likely increase in risk of hazards ratio 1.5 or less. Several new studies have used recently proposed recommendations for analysis or other innovative methodological approaches , although as with all observational data, the possibility of uncontrolled or residual confounding remains. The growing, generally reassuring evidence about other hormonal contraceptive methods, including other injectables like NET-EN, stands in contrast to the DMPA-specific findings. An important next step is for WHO to determine whether these concerns warrant a reconsideration of global guidance for DMPA. Modeling studies can be useful in understanding net health impacts of various policy responses in different epidemiological contexts, including the risk of HIV, maternal mortality and morbidity, and access to alternative contraception and HIV prevention methods [2,73–76].
We are grateful to Sharon Achilles for her thoughtful input related to describing potential biological mechanisms, and to all study investigators who provided additional information about their analyses. WHO provided support for the writing of this systmatic review and for the writing group to attend a working meeting in Geneva, Switzerland in October 2015. D.J.W. was partially funded by NIH DP2-HD-08-4070. The review was conducted independently of the WHO guidance development process; and conclusions represent the independent opinions of the authors. The findings and conclusions in this article do not necessarily reflect the positions and policies of the donor.
Role of authors: The World Health Organization (J.N.K. and P.S.S.) initiated the idea to conduct this systematic review update. C.B.P. led the conduct of the systematic review, including conducting the systematic literature search and drafting the manuscript. C.B.P., K.M.C., and P.C.H. screened titles, abstracts, and full-text manuscripts to determine study inclusion. S.J.P. conducted the statistical meta-analysis. All coauthors (C.B.P., K.M.C., P.C.H., S.J.P., T.C., J.N.K., D.J.W., and P.S.S.) participated in framing the study question, developing the quality criteria, abstracting study information and assessing study quality, interpreting the data, and contributing to the writing and editing of the manuscript.
Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official positions of the Guttmacher Institute, the Centers for Disease Control and Prevention, the World Health Organization, the National Institutes of Health, or other institutions with which the authors are affiliated.
Conflicts of interest
C.B.P. worked at USAID between 2011 and 2014, led previous systematic reviews on this topic, and participated in preliminary discussions considering the ECHO trial. P.C.H. served as a reviewer for potential funders of the ECHO protocol to inform their funding decision. S.J.P. participated in the inception of the ECHO trial. T.C., J.N.K., and P.S.S. are current members of the ECHO trial consortium. We do not feel that participation in these activities influenced our work on this systematic review. K.M.C. and D.J.W. have nothing to declare.
1. Polis CB, Phillips SJ, Curtis KM, Westreich DJ, Steyn PS, Raymond E, et al Hormonal contraceptive methods and risk of HIV acquisition in women: a systematic review of epidemiological evidence
2. Butler AR, Smith JA, Polis CB, Gregson S, Stanton D, Hallett TB. Modelling the global competing risks of a potential interaction between injectable hormonal contraception and HIV risk
3. Alkema L, Chou D, Hogan D, Zhang S, Moller AB, Gemmill A, et al Global, regional, and national levels and trends in maternal mortality between 1990 and 2015, with scenario-based projections to 2030: a systematic analysis by the UN Maternal Mortality Estimation Inter-Agency Group
4. Schelar E, Polis CB, Essam T, Looker KJ, Bruni L, Chrisman CJ, et al Multipurpose prevention technologies for sexual and reproductive health: mapping global needs for introduction of new preventive products
5. Blish CA, Baeten JM. Hormonal contraception and HIV-1 transmission
. Am J Reprod Immunol
6. Hel Z, Stringer E, Mestecky J. Sex steroid hormones, hormonal contraception, and the immunobiology of human immunodeficiency virus-1 infection
. Endocr Rev
7. Achilles SL, Hillier SL. The complexity of contraceptives: understanding their impact on genital immune cells and vaginal microbiota
2013; 27 (suppl 1):S5–S15.
8. Hickey M, Marino JL, Tachedjian G. Critical review: mechanisms of HIV transmission in Depo-Provera users: the likely role of hypoestrogenism
. J Acquir Immune Defic Syndr
9. Fichorova RN, Chen PL, Morrison CS, Doncel GF, Mendonca K, Kwok C, et al The contribution of cervicovaginal infections to the immunomodulatory effects of hormonal contraception
10. World Health Organization. Medical eligibility criteria for contraceptive use
. 5th edGeneva, Switzerland: World Health Organization; 2015.
11. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement
. PLoS Med
12. Veritas Health Innovation. Covidence Systematic Review Software
. Melbourne, Australia: Veritas Health Innovation; 2015.
13. Polis CB, Westreich D, Balkus JE, Heffron R. Assessing the effect of hormonal contraception on HIV acquisition in observational data: challenges and recommended analytic approaches
2013; 27 (suppl 1):S35–S43.
14. Hernan MA. The hazards of hazard ratios
15. DerSimonian R, Laird N. Meta-analysis in clinical trials
. Control Clin Trials
16. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses
17. Van Damme L, Corneli A, Ahmed K, Agot K, Lombaard J, Kapiga S, et al Preexposure prophylaxis for HIV infection among African women
. N Engl J Med
18. Masese L, Baeten JM, Richardson BA, Bukusi E, John-Stewart G, Graham SM, et al Changes in the contribution of genital tract infections to HIV acquisition among Kenyan high-risk women from 1993 to 2012
19. Ralph LJ, McCoy SI, Shiu K, Padian NS. Hormonal contraceptive use and women's risk of HIV acquisition: a meta-analysis of observational studies
. Lancet Infect Dis
20. Brind J, Condly SJ, Mosher SW, Morse AR, Kimball J. Risk of HIV infection in depot-medroxyprogesterone acetate (DMPA) users: a systematic review and meta-analysis
. Issues Law Med
21. Crook AM, Ford D, Gafos M, Hayes R, Kamali A, Kapiga S, et al Injectable and oral contraceptives and risk of HIV acquisition in women: an analysis of data from the MDP301 trial
. Hum Reprod
22. Dube K, Zango A, van de Wijgert J, Meque I, Ferro JJ, Cumbe F, et al HIV incidence in a cohort of women at higher risk in Beira, Mozambique: prospective study 2009–2012
. PLoS One
23. Feldblum PJ, Enosse S, Dube K, Arnaldo P, Muluana C, Banze R, et al HIV prevalence and incidence in a cohort of women at higher risk for HIV acquisition in Chokwe, southern Mozambique
. PLoS One
24. Kapiga SH, Ewings FM, Ao T, Chilongani J, Mongi A, Baisley K, et al The epidemiology of HIV and HSV-2 infections among women participating in microbicide and vaccine feasibility studies in Northern Tanzania
. PLoS One
25. McKinnon LR, Izulla P, Nagelkerke N, Munyao J, Wanjiru T, Shaw SY, et al Risk factors for HIV acquisition in a prospective Nairobi-based female sex worker cohort
. AIDS Behav
26. Morrison CS, Chen PL, Kwok C, Baeten JM, Brown J, Crook AM, et al Hormonal contraception and the risk of HIV acquisition: an individual participant data meta-analysis
. PLoS Med
27. Wall KM, Kilembe W, Vwalika B, Htee KN, Brill I, Chomba E, et al Hormonal contraception does not increase women's HIV acquisition risk in Zambian discordant couples, 1994–2012
28. Byrne EH, Anahtar MN, Cohen KE, Moodley A, Padavattan N, Ismail N, et al Association between injectable progestin-only contraceptives and HIV acquisition and HIV target cell frequency in the female genital tract in South African women: a prospective cohort study
. Lancet Infect Dis
29. Balkus JE, Brown ER, Hillier SL, Coletti A, Ramjee G, Mgodi N, et al Oral and injectable contraceptive use and HIV acquisition risk among women in four African countries: a secondary analysis of data from a microbicide trial
30. Noguchi LM, Richardson BA, Baeten JM, Hillier SL, Balkus JE, Chirenje ZM, et al Risk of HIV-1 acquisition among women who use different types of injectable progestin contraception in South Africa: a prospective cohort study
. Lancet HIV
31. Wand H, Ramjee G. The effects of injectable hormonal contraceptives on HIV seroconversion and on sexually transmitted infections
32. Kaul R, Kimani J, Nagelkerke NJ, Fonck K, Ngugi EN, Keli F, et al Monthly antibiotic chemoprophylaxis and incidence of sexually transmitted infections and HIV-1 infection in Kenyan sex workers: a randomized controlled trial
33. Vallely A, Kasindi S, Hambleton IR, Knight L, Chirwa T, Balira R, et al Microbicides development program, Tanzania-baseline characteristics of an occupational cohort and reattendance at 3 months
. Sex Transm Dis
34. Delany-Moretlwe S, Rees H. Tshireletso study for women's health. Microbicide feasibility study. Protocol
. Hillbrow, South Africa: Reproductive Health Research Unit, University of Witwatersrand; 2010.
36. Vandepitte J, Bukenya J, Weiss HA, Nakubulwa S, Francis SC, Hughes P, et al HIV and other sexually transmitted infections in a cohort of women involved in high-risk sexual behavior in Kampala, Uganda
. Sex Transm Dis
37. Abdool Karim Q, Abdool Karim SS, Frohlich JA, Grobler AC, Baxter C, Mansoor LE, et al Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women
38. Morrison CS. Personal communication: subanalysis of previously unpublished data in IPD meta-analysis
39. Baeten JM, Benki S, Chohan V, Lavreys L, McClelland RS, Mandaliya K, et al Hormonal contraceptive use, herpes simplex virus infection, and risk of HIV-1 acquisition among Kenyan women
40. Bulterys M, Chao A, Habimana P, Dushimimana A, Nawrocki P, Saah A. Incident HIV-1 infection in a cohort of young women in Butare, Rwanda
41. Feldblum PJ, Lie CC, Weaver MA, Van DL, Halpern V, Adeiga A, et al Baseline factors associated with incident HIV and STI in four microbicide trials
. Sex Transm Dis
42. Heffron R, Donnell D, Rees H, Celum C, Mugo N, Were E, et al Use of hormonal contraceptives and risk of HIV-1 transmission: a prospective cohort study
. Lancet Infect Dis
43. Heffron R, Rees H, Mugo N, Baeten J. Authors’ reply: use of hormonal contraceptives and risk of HIV-1 transmission
. Lancet Infect Dis
44. Kapiga SH, Lyamuya EF, Lwihula GK, Hunter DJ. The incidence of HIV infection among women using family planning methods in Dar es Salaam, Tanzania
45. Kiddugavu M, Makumbi F, Wawer MJ, Serwadda D, Sewankambo NK, Wabwire-Mangen F, et al Hormonal contraceptive use and HIV-1 infection in a population-based cohort in Rakai, Uganda
46. Kilmarx PH, Limpakarnjanarat K, Mastro TD, Saisorn S, Kaewkungwal J, Korattana S, et al HIV-1 seroconversion in a prospective study of female sex workers in northern Thailand: continued high incidence among brothel-based women
47. Kleinschmidt I, Rees H, Delany S, Smith D, Dinat N, Nkala B, et al Injectable progestin contraceptive use and risk of HIV infection in a South African family planning cohort
48. Kumwenda NI, Kumwenda J, Kafulafula G, Makanani B, Taulo F, Nkhoma C, et al HIV-1 incidence among women of reproductive age in Malawi
. Int J STD AIDS
49. Laga M, Manoka A, Kivuvu M, Malele B, Tuliza M, Nzila N, et al Nonulcerative sexually transmitted diseases as risk factors for HIV-1 transmission in women: results from a cohort study
50. Lutalo T, Musoke R, Kong X, Makumbi F, Serwadda D, Nalugoda F, et al Effects of hormonal contraceptive use on HIV acquisition and transmission among HIV-discordant couples
2013; 27 (suppl 1):S27–S34.
51. McCoy SI, Zheng W, Montgomery ET, Blanchard K, van der Straten A, de Bruyn G, et al Oral and injectable contraception use and risk of HIV acquisition among women in sub-Saharan Africa
52. Morrison CS, Chen P, Kwok C, Richardson BA, Chipato T, Mugerwa R, et al Hormonal contraception and HIV acquisition: reanalysis using marginal structural modeling
53. Morrison CS, Richardson BA, Mmiro F, Chipato T, Celentano DD, Luoto J, et al Hormonal contraception and the risk of HIV acquisition
54. Lavreys L, Baeten JM, Martin HL, Overbaugh J, Mandaliya K, Ndinya-Achola JO, et al Hormonal contraception and risk of HIV-1 acquisition: results of a 10-year prospective study
55. Morrison CS, Skoler-Karpoff S, Kwok C, Chen PL, van de Wijgert J, Gehret-Plagianos M, et al Hormonal contraception and the risk of HIV acquisition among women in South Africa
56. Myer L, Denny L, Wright TC, Kuhn L. Prospective study of hormonal contraception and women's risk of HIV infection in South Africa
. Int J Epidemiol
57. Plummer FA, Simonsen JN, Cameron DW, Ndinya-Achola JO, Kreiss JK, Gakinya MN, et al Cofactors in male-female sexual transmission of human immunodeficiency virus type 1
. J Infect Dis
58. Reid SE, Dai JY, Wang J, Sichalwe BN, Akpomiemie G, Cowan FM, et al Pregnancy, contraceptive use, and HIV acquisition in HPTN 039: relevance for HIV prevention trials among African women
. J Acquir Immune Defic Syndr
59. Saracco A, Musicco M, Nicolosi A, Angarano G, Arici C, Gavazzeni G, et al Man-to-woman sexual transmission of HIV: longitudinal study of 343 steady partners of infected men
. J Acquir Immune Defic Syndr
60. Watson-Jones D, Baisley K, Weiss HA, Tanton C, Changalucha J, Everett D, et al Risk factors for HIV incidence in women participating in an HSV suppressive treatment trial in Tanzania
61. Sinei SK, Fortney JA, Kigondu CS, Feldblum PJ, Kuyoh M, Allen MY, et al Contraceptive use and HIV infection in Kenyan family planning clinic attenders
. Int J STD AIDS
62. Ungchusak K, Rehle T, Thammapornpilap P, Spiegelman D, Brinkmann U, Siraprapasiri T. Determinants of HIV infection among female commercial sex workers in northeastern Thailand: results from a longitudinal study
. J Acquir Immune Defic Syndr Hum Retrovirol
63. Wasserstein RL, Lazar NA. The ASA's statement on p-values: context, process, and purpose
. Am Stat
64. McCoy SI, Ralph LJ, Padian NS, Minnis AM. Are hormonal contraceptive users more likely to misreport unprotected sex? Evidence from a biomarker validation study in Zimbabwe
. AIDS Behav
65. Smit J, Gray A, McFadyen L, Zuma K. Counting the costs: comparing depot medroxyprogesterone acetate and norethisterone oenanthate utilisation patterns in South Africa
. BMC Health Serv Res
66. Morroni C, Myer L, Moss M, Hoffman M. Preferences between injectable contraceptive methods among South African women
67. Grabowski MK, Gray RH, Makumbi F, Kagaayi J, Redd AD, Kigozi G, et al Use of injectable hormonal contraception and women's risk of herpes simplex virus type 2 acquisition: a prospective study of couples in Rakai, Uganda
. Lancet Glob Health
68. Borgdorff H, Verwijs MC, Wit FW, Tsivtsivadze E, Ndayisaba GF, Verhelst R, et al The impact of hormonal contraception and pregnancy on sexually transmitted infections and on cervicovaginal microbiota in African sex workers
. Sex Transm Dis
69. Egger M, Smith GD, Schneider M. In: Egger M, Smith GD, Altman DG. Systematic reviews of observational studies
. BMJ Publishing Group, Systematic reviews in healthcare: meta-analysis in context
70. Senn SJ. Overstating the evidence: double counting in meta-analysis and related problems
. BMC Med Res Methodol
71. Egger M, Schneider M, Davey Smith G. Spurious precision? Meta-analysis of observational studies
72. Polis CB, Curtis KM. Use of hormonal contraceptives and HIV acquisition in women: a systematic review of the epidemiological evidence
. Lancet Infect Dis
73. Rodriguez MI, Reeves MF, Caughey AB. Evaluating the competing risks of HIV acquisition and maternal mortality in Africa: a decision analysis
74. Sokat KY, Armbruster B. Implications of switching away from injectable hormonal contraceptives on the HIV epidemic
. Socioecon Plann Sci
75. Jain AK. Hormonal contraception and HIV acquisition risk: implications for individual users and public policies
76. Jain AK. Erratum to: Hormonal contraception and HIV acquisition risk: implications for individual users and public policies
77. Martin HL Jr, Nyange PM, Richardson BA, Lavreys L, Mandaliya K, Jackson DJ, et al Hormonal contraception, sexually transmitted diseases, and risk of heterosexual transmission of human immunodeficiency virus type 1
. J Infect Dis
contraceptive implants; depot medroxyprogesterone acetate; HIV acquisition; hormonal contraception; injectable contraception; norethisterone enanthate; oral contraception; systematic review
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