Clinical issues and debates in contraception for women and adolescents living with HIV Andrew Lofts Gray Division of Pharmacology Discipline of Pharmaceutical Sciences University of KwaZulu-Natal, Durban

The key clinical questions Which hormonal contraceptives (HC) should be used together with antiretroviral therapy (ART)? Which implies, which should NOT be used? How can women’s choices be accommodated with respect to contraception (while on ART)? What do we know about comparative effectiveness of HC options with ART? (some of the same questions may need to be asked in relation to women using PrEP)

A particularly high burden among young women

What has changed? The “typical” patient on ART has changed and will continue to change More diverse in age Including adolescents, young women, older women – representing the entire spectrum of contraceptive needs (delaying/spacing/long-term) Healthier Identified earlier, initiating ART earlier and at higher CD4 counts – needing the entire range of reproductive health options

What has changed?(2) The “typical” patient on ART has changed and will continue to change - contd More diverse in terms of ART regimen Despite the global dominance of a public health-inspired standardised regimen, more women will need 2nd and 3rd line options in time New ART regimens continue to be developed, and may replace existing options – fewer OR new drug-drug interactions with HC

What has changed?(3) There are new “patients” on ARVs PrEP use in HIV(-) women, potentially in adolescents and young women There are increasingly diverse contraceptive options, even in resource constrained settings WHO Model EML 2015 now lists 10 hormonal products (2 with a square box symbol) + IUCD + condoms Women will need to switch between methods at different times Taking away an option needs to be done carefully, if at all

What we don’t know… “Evidence indicates that fertility increases after approximately the first year on ART, and that while the fertility deficit of HIV-positive women is shrinking, their fertility remains below that of HIV-negative women. These findings, however, were based on limited data mostly during the period 2005-2010 when ART scaled up.” Yeatman et al. Impact of ART on the Fertility of HIV-Positive Women in Sub-Saharan Africa. TMIH 2016 doi: 10.1111/tmi.12747

What we do know….

Entrenched in global guidance “Family planning reduces the risk of unintended pregnancy, contributes to lower rates of maternal and infant mortality and morbidity, reduces the number of infants exposed to HIV perinatally, and empowers women to have more control over their reproductive health.” “A commitment by programmes to respecting reproductive and human rights, integrating family planning and HIV prevention, and offering testing and treatment services is essential to meet the sexual and reproductive health needs of women, couples, families and communities.” “Women living in low- and middle-income countries should have more choices for highly effective contraception than are currently available.”

We still need …. AND AND AND Detailed PK data on drug-drug interactions between HC and all ARVs Data on pregnancy outcomes when different contraceptive options are used, at scale, by women who are taking ART under “typical use” conditions Data on particular vulnerable groups, including adolescents and sex workers Implementation research, including how to improve condom use AND AND AND

Tomorrow Most important outcome for contraceptive drug interactions is pregnancy, but few studies have reported pregnancy as an outcome. Most significant interactions appear to be in women using HC + EFV-containing cART, but data are limited. Current published data do not support limiting women’s access to any hormonal contraceptives. Women taking cART or PrEP should have access to the full range of hormonal contraceptive options, and be enabled to make informed decisions about their options.

Conclusion There is still a need for clear, unambiguous and evidence-informed guidance that respects and entrenches women’s reproductive health choices and recognises the differences in their needs at different times of their lives, even when (especially when) living with HIV.