Wellcome Trust and the Bill & Melinda Gates Foundation.

PMTCT Option B+ has been recommended by the World Health Organization since 2012 to reduce vertical transmission, however numerous adherence challenges remain.We conducted a qualitative study at baseline using six focus group discussions and 14 in-depth interviews to explore knowledge, beliefs, attitudes and challenges towards the Option B+ strategy for PMTCT among HIV-infected pregnant and post-partum women and health workers engaged in Uganda's national Option B+ PMTCT programme. Data were analysed using a thematic approach to capture latent and manifest content with the social ecological model as a theoretic foundation in order to make contextual sense of key stakeholders' needs for an effective Option B+ intervention.Overall, among all study participants, we found multi-level barriers to adhering to Option B+ cutting across all levels of the social ecological model (SEM). In line with the SEM, our study revealed barriers at personal, relational, organizational and societal levels. Some personal beliefs such as that the baby's health is more important that the mother's, organizational (negative attitudes and behavior of health workers), structural such as poverty, work conflicts, fear and lack of disclosure related to community stigma were all critical obstacles to women adhering to the Option B+ programme. We found that both health workers and participants in the programme have a relatively clear understanding of the benefits of adhering to their treatment; though a more nuanced understanding and thus emphasis in counselling on side effects, is critical to helping patients adhere.

Background Viral load (VL) testing is key in monitoring adherence to antiretroviral therapy (ART) and documenting HIV treatment response. As per HIV treatment guidelines in Uganda, the first VL test is recommended 6 months after initiation of ART. Undetectable VL (uVL) at ART initiation may be helpful in detecting elite controllers in the absence of previous ART use. We investigated viral suppression at ART initiation among a cohort of HIV-positive pregnant women enrolled in the Friends for Life Circles (FLC) for Option B+ randomized controlled trial (RCT). Methods Pregnant women ≥ 18 years of age testing positive for HIV at their first antenatal care visit and starting on ART Option B+ as per the National PMTCT Program guidelines were enrolled into the FLC for Option B+ RCT in urban Kampala and rural Mityana districts of Uganda. Each participant had whole blood samples collected at enrolment to assess baseline VL. Plasma HIV-1 RNA was quantified using COBAS Ampliprep /COBAS Taqman. Baseline VL below 400 RNA copies/ml was considered as viral suppression while baseline VL below 20 RNA copies/ml was considered uVL. Results The mean duration from the date of ART initiation to time of sample collection for baseline VL assessment was 4.4 days (SD 3.6). Of the 532 HIV-positive pregnant women enrolled in the FLC for Option B+ study and newly starting Option B+ without a self-reported history of prior ART use, 29 (5.5%) had uVL and 113 (21.4%) had suppressed VL at baseline. There was no association between participants’ age, gravidity, marital status, mean monthly income, educational level, disclosure of HIV status to partner, and uVL or viral suppression at baseline. However, non-disclosure of HIV status to any other person was associated with decreased odds of viral suppression at baseline (OR 0.640; 0.416–0.982). Conclusion Twenty-one percent of HIV-positive Ugandan pregnant women initiating ART (Option B+) showed virological suppression at baseline and were presumed to be “elite controllers” or to have misreported being ART-naive. Further studies are needed to better understand the biologic mechanisms of elite controllers among pregnant women as well as to differentiate elite controllers from concealed ART use. Trial Registration The trial was registered as NCT02515370 (04/08/2015) on Clinicaltrials.gov.

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Background Women are under-represented in many mid-career infectious diseases research fellowships, including a TDR fellowship for low- and middle-income country (LMIC) researchers. TDR solicited creative ideas as part of a challenge contest to increase the number of women fellowship applicants. The purpose of this study is to examine themes from submitted ideas and the impact of implementing the top three ideas on the number of women applicants. Methods We solicited ideas for modifying the TDR fellowship using a crowdsourcing challenge. Then we used a mixed methods approach to evaluate texts submitted in response to the challenge. The qualitative analysis identified themes from eligible submissions. The quantitative analysis examined the mean score (1–10 scale) assigned to submitted ideas and also the number of eligible women applicants before (2014–7) and after (2018) implementing the top three ideas. Results We received 311 ideas on improving women’s participation in this fellowship from 63 countries. Among all ideas, 282 (91%) were from women and 286 (92%) were from low- and middle-income countries (LMICs). Thirty-three (17%) ideas received an overall mean score of 7.0 or greater. The top three ideas included enhanced social media communication targeting women, improving career mentorship, and creating a nomination system to nudge women applicants. These ideas were implemented as part of the 2018 fellowship application cycle. The number of eligible women applicants increased from 11 in 2016 to 48 in 2018. The number of eligible men applicants increased from 55 in 2016 to 114 in 2018. Women represent 44% (8/18) of the 2018 cohort. Conclusion This suggests that the challenge contest resulted in strong participation from women in LMICs. The three top ideas likely contributed to a greater number of women applicants to this mid-career fellowship. Further ways of enhancing women’s participation in global health training are needed.

Background: Adolescent girls and young women in Uganda face numerous public health challenges including high HIV prevalence, teenage pregnancies, poor sexual and reproductive health rights, child marriage, and violence. Objectives: This evidence review explores which interventions focusing on the empowerment of adolescent girls and young women to address these challenges are suitable for Ugandan policy. Methods: We reviewed the literature to identify experimental studies and systematic reviews of interventions which improve sexual and reproductive health outcomes and/or prevent violence in adolescent girls and young women in low- and middle-income countries (LMICs). Two authors independently reviewed the studies identified through a comprehensive search strategy and assessed their quality. From this evidence base, two policy options were explored in depth considering benefits, harms, equity impacts, and costs, given the Ugandan context.Results: The screen yielded 47 studies, of which 12 remained after applying inclusion and exclusion criteria and relevance, applicability and quality assessment. Feasible policy options included: a vertical cash-incentive approach at a national or local level to support girls’ attainment of education; and a horizontal integrated community approach focusing on skills and knowledge building. A combination of both is recommended for young female empowerment in Uganda, allowing for the full range of socio-cultural and economic drivers to be targeted.Conclusion: Research into the link between female empowerment and sexual and reproductive health outcomes is still in early development. This review contributes to evidence on this topic and outlines an approach that is potentially suitable for adoption across similar LMICs in Africa. Keywords: Sexual health; health policy; women's health.

Background: Pre-treatment HIV drug resistance is a threat to elimination of mother to child HIV transmission and could lead to virological failure among HIV-positive pregnant women. We analysed genotypic HIV drug resistance (HIVDR) of baseline samples of participants enrolled in the Option B+ clinical trial in Uganda.Methods: HIV-infected pregnant women attending antenatal care were enrolled from Uganda’s National Referral Hospital (Mulago) and Mityana District general hospital and surrounding health centers (HCs). Genotypic HIV testing was performed on blood samples from the first 135 enrolled women out of a subset of 136 participants (25%) who had a baseline VL>1000 copies/mL as one sample failed to amplify.Results: 159/540 (29.4%) had a VL < 1000 copies/ml and 381/540 (70.6%) had a VL >1,000 copies/ml. Of the women with VL>1000 copies/ml, 32 (23.7%) had resistance mutations including 29/135 (21.5%) NNRTI mutations, 6/135 (4.4%) NRTI mutations and 3/135 (2.2%) had both NNRTI and NRTI mutations. The most common NNRTI resistance mutations were: K103KN (5), K103N (5), V179T (4) and E138A (4).Conclusions: One quarter of the HIV-infected pregnant women in this trial at baseline had NNRTI genotypic resistance mutations. Our findings support new WHO guidelines for first-line ART that were changed to dolutegravir-based regimens.

Introduction: Despite scale up of Option B+, long-term retention of women in HIV care during pregnancy and the postpartum period remains an important challenge. We compared adherence to clinic appointments and  antiretroviral therapy (ART) at different follow-up time points between enrolment and 24 months postpartum among pregnant women living with HIV and initiating Option B+ randomized to a peer group support, community-based drug distribution and income-generating intervention called “Friends for Life Circles” (FLCs) versus the standard of care (SOC). Methods: Between 16 May 2016 and 12 September 2017, 540 ART-naïve pregnant women living with HIV at urban and rural health facilities in Uganda were enrolled in the study. Participants were randomized 1:1 to the FLC intervention or SOC and assessed for adherence to prevention of mother to child HIV transmission (PMTCT) clinic appointments at 6 weeks, 12 and 24 months postpartum, self-reported adherence to ART at 6 weeks, 6 and 24 months postpartum validated by plasma HIV-1 RNA viral load (VL) measured at the same time points, and HIV status and HIV-free survival of infants at 18 months postpartum. We used Log-rank and Chi-Square p-values to test the equality of Kaplan-Meier survival probabilities and hazard rates (HR) for failure to retain in care for any reason by study arm. Results: There was no significant difference  in adherence to PMTCT clinic visits or to ART or in median viral loads between FLC and SOC arms at any follow-up time points. Retention in care through the end of study was high in both arms but significantly higher among participants randomized to FLC (86.7%) compared to SOC (79.3%), p=0.022. The adjusted HR of visit dropout was 2.5 times greater among participants randomized to SOC compared to FLC (aHR=2.498, 95% CI: 1.417 – 4.406, p=0.002). Median VL remained < 400 copies/ml in both arms at 6 weeks, 6 and 24 months postpartum. Conclusions: Our findings suggest that programmatic interventions that provide group support, community based ART distribution and income-generation activities may contribute to retention in PMTCT care, HIV-free survival of children born to women living with HIV, and to the elimination of mother to child HIV transmission (MTCT).