HIV-1 Risk and Prevention Strategies for Women during Pregnancy and Postpartum

Thesis (Ph.D.)--University of Washington, 2017-12HIV-1 is the leading cause of death worldwide among women of reproductive age, and this group is a priority to reach with effective HIV-1 prevention. There is great potential to provide HIV-1 interventions to women during the periconception, pregnancy, and postpartum periods by leveraging existing healthcare settings that serve women and couples at high risk of HIV-1 acquisition. These opportunities include integration of HIV-1 prevention strategies within antenatal and postnatal care programs in settings with high HIV-1 prevalence and inclusion of safer conception programs within clinical HIV-1 care for HIV-1 affected individuals and couples desiring children. Specifically, antiretrovirals, as PrEP used by HIV-1 uninfected people and ART used by HIV-1 infected people, are highly effective and important for women and couples, especially those planning and experiencing pregnancy. The aims within this dissertation address questions regarding HIV-1 risk and implementation of antiretrovirals for HIV-1 prevention among women and their partners during reproductive stages, including: quantifying the risk of female HIV-1 acquisition in different reproductive stages, making the case for PrEP as a highly efficacious HIV-1 strategy for women, and describing fertility intentions and willingness to use safer conception strategies during pregnancy attempts among HIV-1 infected individuals. Previous studies have shown that pregnancy and postpartum are periods with heightened HIV-1 acquisition risk for women, but it is not clear whether this is primarily driven by biological or behavioral factors. We have addressed this gap by using robust data from two longitudinal studies to estimate the per coital act probability of female HIV-1 acquisition during the early pregnancy, late pregnancy, and postpartum stages, relative to time periods to unrelated to pregnancy. We found that the risk of HIV-1 transmission per coital act steadily increased pregnancy and was highest during postpartum, even after accounting for sexual behavior, PrEP, and HIV-1 viral load, suggesting that biological changes during these periods increase HIV-1 risk. Conflicting results and conclusions from the initial randomized clinical trials that assessed efficacy of PrEP for HIV-1 prevention among women has spurred debate about whether PrEP is a strategy that women will use effectively. This debate has delayed the initiation of programs to deliver PrEP to women, and specifically has been a barrier to the integration of PrEP into antenatal and postnatal care where it has the potential to reach women who most need enhanced HIV-1 prevention. We have objectively assessed and synthesized existing evidence of PrEP efficacy among women and made a conclusive case that PrEP is an effective HIV-1 prevention strategy for women. Couples affected by HIV-1 with fertility desires experience heightened vulnerability to HIV-1 acquisition when they forgo condom use during pregnancy attempts. “Safer conception” is a risk reduction approach where HIV-1 serodiscordant couples use one or more strategies to reduce the risk of HIV-1 transmission and optimize fertility during pregnancy attempts. We have contributed to the growing demand for information on safer conception with a cross-sectional study to describe fertility intentions and preferences for safer conception strategies, including PrEP and ART, among HIV-1 infected individuals in Seattle, WA. The collective results from this dissertation provide evidence for the urgent need to enhance HIV-1 prevention during pregnancy and the postpartum period, and advance global and local delivery mechanisms for PrEP and ART during periods of heightened risk when they can have substantial HIV-1 prevention impact