Baeten, J., Benki, S., Chohan, V., Lavreys, L., McClelland, R. S., Mandaliya, K., Ndinya‐Achola, J., Jaoko, W., & Overbaugh, J. (2007). Hormonal contraceptive use, herpes simplex virus infection, and risk of HIV-1 acquisition among Kenyan women. AIDS (London, England), 21(13), 1771-1777. https://doi.org/10.1097/QAD.0b013e328270388a
Baeten J, 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. AIDS. 2007;21(13):1771-1777. doi:10.1097/QAD.0b013e328270388a
Baeten, Jared, et al. "Hormonal contraceptive use, herpes simplex virus infection, and risk of HIV-1 acquisition among Kenyan women." AIDS (London, England), vol. 21, no. 13, 2007, pp. 1771-1777.
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Studies of the effect of hormonal contraceptive use on the risk of HIV-1 acquisition have generated conflicting results. A recent study from Uganda and Zimbabwe found that women using hormonal contraception were at increased risk for HIV-1 if they were seronegative for herpes simplex virus type 2 (HSV-2), but not if they were HSV-2 seropositive.
Objective
To explore the effect of HSV-2 infection on the relationship between hormonal contraception and HIV-1 in a high-risk population. Hormonal contraception has previously been associated with increased HIV-1 risk in this population.
Methods
Data were from a prospective cohort study of 1206 HIV-1 seronegative sex workers from Mombasa, Kenya who were followed monthly. Multivariate Cox proportional hazards analyses were used to adjust for demographic and behavioral measures and incident sexually transmitted diseases.
Results
Two hundred and thirty-three women acquired HIV-1 (8.7/100 person-years). HSV-2 prevalence (81%) and incidence (25.4/100 person-years) were high. In multivariate analysis, including adjustment for HSV-2, HIV-1 acquisition was associated with use of oral contraceptive pills [adjusted hazard ratio (HR), 1.46; 95% confidence interval (CI), 1.00-2.13] and depot medroxyprogesterone acetate (adjusted HR, 1.73; 95% CI, 1.28-2.34). The effect of contraception on HIV-1 susceptibility did not differ significantly between HSV-2 seronegative versus seropositive women. HSV-2 infection was associated with elevated HIV-1 risk (adjusted HR, 3.58; 95% CI, 1.64-7.82).
Conclusions
In this group of high-risk African women, hormonal contraception and HSV-2 infection were both associated with increased risk for HIV-1 acquisition. HIV-1 risk associated with hormonal contraceptive use was not related to HSV-2 serostatus.
Peebles K et al., 2021·Clinical infectious diseases : an official publication of the Infectious Diseases Society of America·Free full text on PubMed Central
Limited evidence suggests that the nonhormonal contraceptive copper intrauterine device (Cu-IUD) may increase bacterial vaginosis (BV) risk, possibly due to increased volume and duration of menses, a common side effect of Cu-IUD use. Although increases in bleeding typically resolve within 6-12 months following initiation, evaluations of the association between Cu-IUD and BV have not included more than 6 months of follow-up. This secondary analysis of a human immunodeficiency virus type 1 prevention trial included 2585 African women ages 18-45 followed for up to 33 months. Women reported contraceptive use each month. BV was evaluated by Nugent score in 6-monthly intervals and, if clinically indicated, by Amsel criteria. Andersen-Gill proportional hazards models were used to (1) evaluate BV risk among Cu-IUD users relative to women using no/another nonhormonal contraceptive and (2) test changes in BV frequency before, while using, and following Cu-IUD discontinuation. BV frequency was highest among Cu-IUD users at 153.6 episodes per 100 person-years (95% confidence interval [CI]: 145.2, 162.4). In adjusted models, Cu-IUD users experienced 1.28-fold (95% CI: 1.12, 1.46) higher BV risk relative to women using no/another nonhormonal contraception. Compared to the 6 months prior to initiation, BV risk was 1.52-fold (95% CI: 1.16, 2.00) higher in the first 6 months of Cu-IUD use and remained elevated over 18 months of use (P < .05). Among women who discontinued Cu-IUD, BV frequency was similar to pre-initiation rates within 1 year. Cu-IUD users experienced elevated BV risk that persisted throughout use. Women and their providers may wish to consider BV risk when discussing contraceptive options.
Morrison CS et al., 2015·PLoS Med·Free full text on PubMed Central
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. 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 1,830 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 (I(2) < 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 (p(interaction) = 0.003). Neither age nor herpes simplex virus type 2 infection status modified the HC-HIV relationship. 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.
Heffron R et al., 2012·Lancet Infect Dis·Free full text on PubMed Central
Hormonal contraceptives are used widely but their effects on HIV-1 risk are unclear. We aimed to assess the association between hormonal contraceptive use and risk of HIV-1 acquisition by women and HIV-1 transmission from HIV-1-infected women to their male partners. In this prospective study, we followed up 3790 heterosexual HIV-1-serodiscordant couples participating in two longitudinal studies of HIV-1 incidence in seven African countries. Among injectable and oral hormonal contraceptive users and non-users, we compared rates of HIV-1 acquisition by women and HIV-1 transmission from women to men. The primary outcome measure was HIV-1 seroconversion. We used Cox proportional hazards regression and marginal structural modelling to assess the effect of contraceptive use on HIV-1 risk. Findings: Among 1314 couples in which the HIV-1-seronegative partner was female (median follow-up 18·0 [IQR 12·6-24·2] months), rates of HIV-1 acquisition were 6·61 per 100 person-years in women who used hormonal contraception and 3·78 per 100 person-years in those who did not (adjusted hazard ratio 1·98, 95% CI 1·06-3·68, p=0·03). Among 2476 couples in which the HIV-1-seronegative partner was male (median follow-up 18·7 [IQR 12·8-24·2] months), rates of HIV-1 transmission from women to men were 2·61 per 100 person-years in couples in which women used hormonal contraception and 1·51 per 100 person-years in couples in which women did not use hormonal contraception (adjusted hazard ratio 1·97, 95% CI 1·12-3·45, p=0·02). Marginal structural model analyses generated much the same results to the Cox proportional hazards regression. Interpretation: Women should be counselled about potentially increased risk of HIV-1 acquisition and transmission with hormonal contraception, especially injectable methods, and about the importance of dual protection with condoms to decrease HIV-1 risk. Non-hormonal or low-dose hormonal contraceptive methods should be considered for women with or at-risk for HIV-1. US National Institutes of Health and the Bill & Melinda Gates Foundation.
Combined oral contraceptives (COC) and depot-medroxyprogesterone acetate (DMPA) are among the most widely used family planning methods; their effect on HIV acquisition is not known. To evaluate the effect of COC and DMPA on HIV acquisition and any modifying effects of other sexually transmitted infections. This multicenter prospective cohort study enroled 6109 HIV-uninfected women, aged 18-35 years, from family planning clinics in Uganda, Zimbabwe and Thailand. Participants received HIV testing quarterly for 15-24 months. The risk of HIV acquisition with different contraceptive methods was assessed (excluding Thailand, where there were few HIV cases). HIV infection occurred in 213 African participants (2.8/100 woman-years). Use of neither COC [hazard ratio (HR), 0.99; 95% confidence interval (CI), 0.69-1.42] nor DMPA (HR, 1.25; 95% CI, 0.89-1.78) was associated with risk of HIV acquisition overall, including among participants with cervical or vaginal infections. While absolute risk of HIV acquisition was higher among participants who were seropositive for herpes simplex virus 2 (HSV-2) than in those seronegative at enrolment, among the HSV-2-seronegative participants, both COC (HR, 2.85; 95% CI, 1.39-5.82) and DMPA (HR, 3.97; 95% CI, 1.98-8.00) users had an increased risk of HIV acquisition compared with the non-hormonal group. No association was found between hormonal contraceptive use and HIV acquisition overall. This is reassuring for women needing effective contraception in settings of high HIV prevalence. However, hormonal contraceptive users who were HSV-2 seronegative had an increased risk of HIV acquisition. Additional research is needed to confirm and explain this finding.
Hormonal contraceptives have been associated with increased risk of HIV acquisition. The association between hormonal contraception use and HIV acquisition was assessed in a rural community-based cohort in Rakai District, Uganda. A group of 5117 sexually active HIV-negative women were surveyed at 10 month intervals between 1994 and 1999. Information on demographic and sociobehavioral characteristics, use of hormonal contraception (pill and injectable methods), condoms and the number of sexual partners was obtained by home-based interview. HIV incidence rate ratios (IRR) and 95% confidence intervals (CI) associated with hormonal contraception were estimated by multivariate Poisson regression after adjustment for age, condom use, number of sexual partners, marital status, education and history of genital ulcer disease. At one or more interviews, 16.6% of women reported use of hormonal contraceptives and 23.0% reported condom use. HIV incidence was 2.3/100 person-years in hormonal contraceptive users compared with 1.5/100 person-years in non-hormonal contraceptive users (unadjusted IRR, 1.56; 95% CI, 1.00-2.33). After multivariate adjustment, the IRR associated with hormonal contraceptives was reduced to 0.94 (95% CI, 0.53-1.64). The adjusted IRR was 1.12 (95% CI, 0.48-2.56) with oral contraceptive use and 0.84 (95%CI, 0.41-1.72) with injectable methods. Use of hormonal contraception is not associated with HIV acquisition after adjustment for behavioral confounding.
To evaluate the effect of oral and injectable hormonal contraception on the risk of HIV acquisition among women in South Africa and Zimbabwe.
Secondary data analysis of 4913 sexually active women aged 18-49 years followed for up to 24 months in the Methods for Improving Reproductive Health in Africa (MIRA) phase III effectiveness trial of the diaphragm and lubricant gel for HIV prevention. Participants were interviewed quarterly about contraception and sexual behavior and were tested for pregnancy, HIV, and other sexually transmitted infections. We used a Cox proportional hazards marginal structural model, weighted by the inverse probability of hormonal contraception use, to compare the risk of HIV acquisition among nonpregnant women reporting use of combined oral contraceptive pills (COC), progestin-only pills (POP), and/or injectable hormonal contraception to women not using these methods. During the study, 283 participants seroconverted. Use of oral contraceptives (POP or COC) was not associated with HIV risk [adjusted hazard ratio (HRa) = 0.86, 95% confidence interval (CI) 0.32, 1.78]. Injectable hormonal contraception was associated with a small nonsignificant risk of HIV infection (HR(a) = 1.34, 95% CI 0.75, 2.37). The effect of injectable hormonal contraception was similar in the unweighted site-adjusted only (HR(a) = 1.32, 95% CI 1.00, 1.74) and baseline factor adjusted models (HR(a) = 1.27, 95% CI 0.94, 1.72). In this study, oral contraceptives were not associated with HIV acquisition. There is substantial uncertainty in the effect of injectable hormonal contraception on HIV risk. These findings underscore the importance of dual protection with condoms and the need for diverse contraceptive options for women at risk of HIV infection.
Comparative Studies · Contraception Versus Fertility Awareness
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. We analyzed data from 5567 women aged 16-49 years participating in the Carraguard Phase 3 Efficacy Trial. Participants were interviewed about contraceptive 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. 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 = 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. In this study conducted among South African women, hormonal contraception 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.
Contraception › Oral Contraceptives › Cancer Risk
Jared M Baeten, R Scott McClelland, Walter Jaoko, Julie Overbaugh, Sarah Benki, Vrasha Chohan, Ludo Lavreys, Kishorchandra Mandaliya, Jeckoniah O Ndinya-Achola
J Baeten, W Jaoko, J Overbaugh, S Benki, V Chohan, L Lavreys, K Mandaliya, J Ndinya-Achola
PMID 17690576 17690576 DOI 10.1097/QAD.0b013e328270388a 10.1097/QAD.0b013e328270388a Baeten et al. 2007, Baeten 2007
Cite this article
Baeten, J., Benki, S., Chohan, V., Lavreys, L., McClelland, R. S., Mandaliya, K., Ndinya‐Achola, J., Jaoko, W., & Overbaugh, J. (2007). Hormonal contraceptive use, herpes simplex virus infection, and risk of HIV-1 acquisition among Kenyan women. AIDS (London, England), 21(13), 1771-1777. https://doi.org/10.1097/QAD.0b013e328270388a
Baeten J, 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. AIDS. 2007;21(13):1771-1777. doi:10.1097/QAD.0b013e328270388a
Baeten, Jared, et al. "Hormonal contraceptive use, herpes simplex virus infection, and risk of HIV-1 acquisition among Kenyan women." AIDS (London, England), vol. 21, no. 13, 2007, pp. 1771-1777.
