Adverse pregnancy outcomes, non-retention, eligibility of differentiated care and virologic failure among women living with HIV in prevention of vertical transmission programs

Provision of antiretroviral treatment (ART) to women living with HIV (WLWH) before and during pregnancy is key to prevention of vertical HIV transmission (or prevention of mother-to-child transmission [PMTCT]), including suppressed maternal HIV viral loads (VL) and improved maternal health. Studies have reported that ART use during pregnancy may affect the risks of adverse pregnancy outcomes (APOs), but underlying mechanisms are undefined. Current WHO guidelines recommend all pregnant and breastfeeding WLWH initiate lifelong ART, and prevention of vertical transmission requires women maintain long-term retention in care. However, there is no standard definition to evaluate retention in PMTCT programs and studies have used a wide range of methodologies, making it difficult to compare results comprehensively across different study designs, measurement approaches and follow-up durations. For people living with HIV and stable on ART, differentiated service delivery (DSD) approaches have shown promising health outcomes and implementation benefits, but it is unclear how to build DSD models for breastfeeding women with suppressed VL in PMTCT programs. In the following dissertation aims, we address these questions. In Chapter 2, we evaluated the risks of APOs including stillbirth (SB), preterm birth (PTB) and neonatal death (NND) among pregnant WLWH in Kenya enrolled in PMTCT programs and identified potential predictors of APOs with a focus on HIV-related factors including ART use, sexual and reproductive history and sexual partnership. In Chapter 3, we assessed three aspects of women’s non-retention in care, including loss to follow-up (LTFU), incomplete visit coverage, and late visits, to identify different insights on engagement in care during the peripartum period of WLWH from pregnancy to 24- month postpartum. We also explored factors that influenced non-retention. In Chapter 4, we performed trajectory analysis to describe longitudinal HIV VL patterns among WLWH in 24 months follow-up periods. We also evaluated the proportion of women who would have been classified as DSD-eligible according to the WHO general guidelines, and determined risk factors of subsequent viral failure among DSD-eligible women to inform future DSD implementation in PMTCT programs. We demonstrated that APO was not associated with particular ART regimen or timing of ART initiation, but was associated with maternal viremia, psychosocial stressors, education level, and sexual and reproductive factors. We reported cofactors of non-retention in care may differ depending on which retention measures were assessed, and late visit attendance may be a sentinel indicator of subsequent LTFU. We found most women maintained viral suppression from early postpartum to 24 months and may be suitable for DSD referral, and women with depression, drug resistance and detectable VL may need enhanced services to prevent further VF. This dissertation provides important insights regarding the safety of ART use in pregnancy outcomes, comprehensive monitoring of women’s retention and HIV VL in long-term follow-up, as well as implication of integrating differentiated healthcare services into PMTCT programs.