Extraordinary gains have been made in the last decade toward increasing access to antiretroviral therapy (ART) for HIV. With an eye toward ending the AIDS epidemic by 2030, UNAIDS recently released bold targets related to HIV diagnosis and treatment. By the year 2020, their aim is to have 90 percent of all people living with HIV aware of their status, 90 percent of people diagnosed with HIV receiving sustained ART and 90 percent of people on ART achieving viral suppression. As we move closer to these laudable public health goals, we must also consider how expansion of ART may affect and be affected by other health issues, such as prevention of unintended pregnancy among women living with HIV.
An increasingly important issue is whether certain ART regimens are expected to have drug interactions when used with certain hormonal contraceptive methods. In theory, an interaction could affect the efficacy of either medication or cause side effects or toxicity. If contraceptive efficacy decreases, the chances of contraceptive failure, unintended pregnancy and the accompanying consequences increase. A decrease in ART efficacy could lead to treatment failure, viral resistance and greater likelihood of subsequent HIV transmission. Increases in side effects or toxicity can affect quality of life and medication adherence. Yet, despite the importance of this issue, relatively few studies (particularly those with clinical outcomes such as ovulation, pregnancy or treatment failure) have been conducted.
In July 2014, based upon comprehensive systematic reviews and an expert consultation, the World Health Organization released updated guidance on hormonal contraception and HIV. One component of this guidance focuses on potential drug interactions between various hormonal contraceptive methods and ART. Subsequently, the Office of Population and Reproductive Health at the U.S. Agency for International Development (USAID) and the President’s Emergency Plan for AIDS Relief (PEPFAR) developed a technical brief on drug interactions, with technical assistance from FHI 360.
The current guidance notes that women taking ART are eligible for all hormonal contraceptive methods, but special consideration might be necessary for women using some hormonal methods (combined hormonal methods, progestogen-only pills, norethisterone enanthate (NET-EN), or levonorgestrel (LNG) and etonogestrel (ETG) implants) with certain ART regimens (specifically those containing efavirenz or nevirapine, as well as some protease inhibitors). These combinations are ranked as medical eligibility criteria (MEC) Category 2: The advantages of using that specific contraceptive method (in combination with those specific antiretroviral drugs) generally outweigh the theoretical or proven risks (in this case, because of potentially reduced contraceptive efficacy). For specific details on these potential interactions, interested readers should refer to the documents linked above. For more information on MEC Category meanings, readers should refer to the WHO guidance.
Limited available data suggest that ART efficacy is not impacted by use of hormonal contraceptive methods, and limited data suggest that combined oral contraceptive pills, depot-medroxyprogesterone acetate (DMPA, sometimes called Depo-Provera), and implants are also unlikely to have an impact on ART side effects or toxicity.
This raises an interesting situation with regard to DMPA. Scientific uncertainty exists as to whether DMPA is causally associated with an increased risk of HIV acquisition among HIV-negative women. However, when used by women living with HIV who are on ART, DMPA is not expected to have any drug interactions with ART (unlike oral contraceptive pills and possibly contraceptive implants). Furthermore, ART use greatly reduces the risk of transmission to a sexual partner, which would minimize possible concerns (based on limited data) about DMPA and female-to-male HIV transmission. Therefore, while the scientific community debates how to more definitively assess the impact of DMPA on risk of HIV acquisition in HIV-negative women, including the possibility of a randomized trial, DMPA will likely remain an important option for women living with HIV and using ART, both for their own health and autonomy, and also to reduce perinatal HIV. Other contraceptive options, such as hormonal or non-hormonal IUDs, where appropriate, can also provide important benefits for women on ART.
The global health community must enhance efforts to better understand potential drug interactions between various ART regimens and various methods of hormonal contraception. More than 18 million women currently living with HIV deserve clear, accurate information on which to base lifesaving health care decisions.
Chelsea Polis and Kavita Nanda were both directly involved in writing the two major documents mentioned: the 2014 WHO guidance and the USAID/PEPFAR brief on hormonal contraception and ART.