Hormonal contraceptive methods are highly effective in reducing the risk of pregnancy in women living with HIV whether on antiretroviral therapy (ART) or not, according to an evaluation involving over 5,000 women, Maria Pyra told participants at the recent Eighth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2015). Contrary to limited evidence suggesting ART may reduce the effectiveness of contraceptive methods, notably implants, the data showed implants to be highly effective compared to no contraception and more effective than injectables or oral contraceptive pills.
Use of implants reduced the risk of pregnancy by more than 90% among women on ART as well as women not on ART (adjusted hazard ratio: (aHR) 0.06, 95% CI: 0.01-0.45 and aHR: 0.05, 95% CI: 0.02-0.11, respectively). Pregnancy incidence rates among women not using contraception were 13.2 and 22.5 per 100 women-years for those on and not on ART, respectively.
Pyra stressed the public health imperative of ensuring that women living with HIV who may wish to avoid or postpone pregnancy have access to safe and reliable contraception. The potential for some hormonal contraceptive methods and some antiretrovirals to interact with each other may hypothetically result in diminished efficacy of either medication and/or increased side-effects and toxicity. Any possible decrease in the effectiveness of hormonal contraceptive methods may increase the risk of unintended pregnancy and possible associated negative health outcomes. A decrease in ART efficacy could increase the risk of treatment failure, viral resistance, transmission to sexual partners and infants; and an increase in side-effects will affect the health and quality of life of the woman living with HIV, and possibly treatment adherence.
A limited number of studies have suggested that certain antiretrovirals including protease inhibitors, the non-nucleoside reverse transcriptase inhibitors (NNRTIs) nevirapine and efavirenz and the cobicistat-boosted elvitegravir may diminish the effectiveness of combined (estrogen/progestin) oral, injectable and implant contraceptives. A recently published retrospective chart review found a higher pregnancy rate among women using implants and efavirenz-based ART compared to women taking a non efavirenz-based ART regimen. Few data are available regarding the effect of hormonal contraceptive methods on the efficacy of ART. However, pharmacokinetic data suggest that oral contraceptives, injectables or implants are unlikely to affect ART toxicity,
Pyra and colleagues combined data from 5,153 women living with HIV who participated in three longitudinal studies (Partners in Prevention HSV/HIV Transmission study, Couples Observational study and Partners PrEP study) in Uganda, Kenya, Rwanda, Tanzania, Zambia, Botswana and South Africa, over an eight-year period to calculate incident pregnancy rates among women using different contraceptive methods (implant, injectable and oral).
These rates were then compared to rates among women using no contraception. (The three studies evaluated the risks of HIV acquisition and transmission among discordant couples including the effect of hormonal contraceptives; the Couples Observational study looked at the immune correlates of HIV protection.)
Controlling for confounding factors, the interaction between each contraceptive method and ART use was assessed to determine if ART reduced contraceptive effectiveness. The women were relatively young with a median age of 29, healthy (over 50% had CD4 cell counts greater than 500 and had not taken ART at enrolment.
Median follow-up was 1.8 years (interquartile range [IQR]: 1.2-2.3years). Among the more than 50% of women ever using contraceptives, 9% used implants, 41% injectables (notably DMPA (Depo-Provera)) and 15% took oral contraceptive pills. During the follow-up period, 31% of women ever took ART, 23% of whom took neviripine and 5% efavirenz. Just under a quarter (24%) of women became pregnant.
Implants were highly effective in reducing the risk of pregnancy among women on and not on ART, with an incident rate of 1.1 and 1.4 per 100 women years, respectively. Shorter-acting methods were effective, but less so than implants. Pregnancy risk was reduced among those using injectables on ART and not on ART by 82% (aHR: 0.18, 95% CI:0.09-0.35) and 80% (aHR: 0.20, 95%CI: 0.16-0.24), respectively. Oral contraceptive use reduced the risk of pregnancy among those on ART and not on ART by approximately 60% (aHR: 0.37, 95% CI: 0.15-0.91 and aHR: 0.36, 95% CI: 0.28-0.47, respectively).
Pyra and colleagues found no statistical evidence that ART use including nevirapine reduced contraceptive effectiveness. When limited to efavirenz, all methods showed reduced effectiveness. However, there was no statistically significant difference when compared to women on no ART. Pyra concluded that hormonal contraceptives, notably implants and injectables, are effective for women living with HIV on ART. Pyra concluded data on real-world hormonal contraception effectiveness are important in family planning guidelines for women living with HIV.
Background: Ensuring safe, effective contraception for women with HIV is a public health imperative. Some data has suggested that antiretroviral therapy (ART) may diminish contraceptive effectiveness, particularly for the combination of implants and NNRTIs, such as nevirapine (NVP) and efavirenz (EFV). In this study, we determined the effectiveness of different hormonal contraceptives by women’s ART use, determined by the clinical endpoint of pregnancy. Methods: Data from 5,153 HIV-infected women participating in three longitudinal studies (Partners in Prevention HSV/HIV Transmission Study, Couples Observation Study, and Partners PrEP Study) from seven countries in Africa between 2004-2012 were used for this analysis. All women were in serodiscordant couples and were not using ART at enrollment. Study visits were conducted quarterly; hormonal contraception and condoms were provided. Visits when women were using non-hormonal methods (diaphragms, IUDs, tubal ligations, or hysterectomies) or were >=50 years old were excluded. Women were censored during each pregnancy and returned to the risk set at the first visit they were not pregnant. Multivariable Cox regression models were used, with pregnancy as a repeated outcome, to test the interaction between each contraceptive method (implant, injectable, oral contraception (OC), or none) and any ART use. Age, CD4 count, site, and study were included a priori; sexual frequency and any condomless sex were added as significant covariates. The analysis was then repeated, restricting ART use to NVP and EFV separately.
Results: 5,153 women contributed 9,266 person-years (median 1.8 years). Participants were young (54% under 30) and healthy (51% CD4 counts >500 cells/mm3) at enrollment. During follow-up 24% of women became pregnant and 31% initiated ART. Pregnancy incidence was 14.8 per 100 person-years overall. Use of implants reduced the risk of pregnancy by more than 90%, both among women on ART and not on ART. Injectables reduced pregnancy risk by ~80% and OCs reduced pregnancy by ~65%, with no statistical difference between women on ART versus women not on ART. There were approximately 1000 person-years of follow-up on NVP and 200 person-years on EFV. There was no evidence of significant effect modification when limiting the analysis to NVP or EFV. However, the estimated effectiveness of all methods was somewhat attenuated among EFV users
Conclusions: In this large evaluation of three prospective studies, modern contraceptive methods remained highly effective in reducing pregnancy risk in HIV-infected women, including those concurrently using ART. While limited evidence from other studies suggests that some ART agents could diminish the effectiveness of contraceptive implants, these data emphasize that implantable contraception is highly effective compared to no contraception and more so than shorter-acting methods such as injectables and oral pills. Follow-up time on EFV was limited and all hormonal methods showed reduced effectiveness among EFV users, though these differences were not statistically significant. These results of real-world hormonal contraception effectiveness are important considerations in determining family planning guidelines for women with HIV.