Long-term retention on antiretroviral treatment after enrolment in prevention of vertical HIV transmission services: a prospective cohort study in Dar es Salaam, Tanzania.

INTRODUCTION: To prevent vertical HIV transmission and ensure healthy mothers and children, pregnant women with HIV must remain on antiretroviral treatment (ART) for life. However, motivation to remain on ART may decline beyond the standard 2-year breastfeeding/postpartum period. We assessed attrition and retention in ART care among women with HIV up to 6 years since enrolment in vertical transmission prevention services in Dar es Salaam, Tanzania. METHODS: A prospective cohort of 22,631 pregnant women with HIV were enrolled in vertical transmission prevention services between January 2015 and December 2017 in routine healthcare settings and followed-up to July 2021. Kaplan-Meier was used to estimate time to ART attrition (died, stopped ART or was lost to follow-up [no show ≥90 days since scheduled appointment]) and the proportion retained in care. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR) of ART attrition in relation to predictors. RESULTS: Participants were followed-up to 6 years for a median of 3 years (IQR: 0.1-4). The overall ART attrition rate was 13.8 per 100 person-years (95% CI: 13.5-14.1), highest in the first year of enrolment at 27.1 (26.3-27.9), thereafter declined to 9.5 (8.9-10.1) in year 3 and 2.7 (2.1-3.5) in year 6. The proportion of women retained in care were 78%, 69%, 63%, 60%, 57% and 56% at 1, 2, 3, 4, 5 and 6 years, respectively. ART attrition was higher in young women aged <20 years (aHR 1.63, 95% CI: 1.38-1.92) as compared to 30-39 year-olds and women enrolled late in the third versus first trimester (aHR 1.29, 95% CI: 1.16-1.44). In contrast, attrition was lower in older women ≥40 years, women who initiated ART before versus during the index pregnancy and women attending higher-level health facilities. CONCLUSIONS: ART attrition among women with HIV remains highest in the first year of enrolment in vertical transmission prevention services and declines markedly following a transition to chronic HIV care. Targeted interventions to improve ART continuity among women with HIV during and beyond prevention of vertical transmission are vital to ending paediatric HIV and keeping women and children alive and healthy.

Resistance-informed versus empirical management of viraemia in children and adolescents with HIV in Lesotho and Tanzania (GIVE MOVE trial): a multisite, open-label randomised controlled trial.

BACKGROUND: Children and adolescents with HIV taking antiretroviral therapy (ART) have high rates of viraemia. We assessed if genotypic resistance testing (GRT) to inform onward treatment improved treatment outcomes in Lesotho and Tanzania, two countries with little access to GRT. METHODS: The Genotype-Informed Versus Empirical Management of Viremia (GIVE MOVE) open-label, parallel-group randomised controlled trial enrolled children and adolescents with HIV between the ages of 6 months and 19 years, taking ART, and with a viral load at least 400 copies per mL. Participants were recruited from ten clinical centres and hospitals in Lesotho and Tanzania. Participants were electronically randomly allocated 1:1 to receive either GRT with expert recommendation (GRT group) or repeat viral-load testing and empirical onward treatment (usual care group). Participants and study staff were not masked, but the endpoint committee and laboratory staff conducting viral-load testing were. Participants in both groups received at least three sessions of enhanced adherence counselling, and in the GRT group, blood for GRT assessed via Sanger sequencing was drawn at enrolment. The composite primary endpoint was death, hospitalisation, a new WHO HIV clinical stage 4 event, or not having documented viral suppression of less than 50 copies per mL at 36 weeks in the modified intention-to-treat population, which excluded participants who were retrospectively found to be ineligible after randomisation. Serious adverse events were analysed in the modified intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT04233242) and the trial status is completed. FINDINGS: Between March 3, 2020, and July 5, 2022, 286 participants were enrolled and 284 were included in the modified intention-to-treat analysis (144 in the GRT group and 140 in the usual care group). Of these participants, 158 (56%) were female and 126 (44%) were male. Five (3%) in the GRT group and four (3%) in the usual care group did not complete follow-up but were included in the primary analysis. The median age across both groups was 14 years (IQR 9-16). The composite primary endpoint occurred in 67 (47%) participants in the GRT group and 73 (52%) in the usual care group (adjusted odds ratio 0·79 [95% CI 0·49 to 1·27]; adjusted risk difference -0·06 [95% CI -0·17 to 0·06]; p=0·34); all participants reaching the composite primary endpoint had no documented viral suppression at 36 weeks. No deaths were recorded, and only one clinical stage 4 event requiring hospitalisation occurred (in the usual care group); this was the only serious adverse event recorded in the study. INTERPRETATION: GRT-informed management did not significantly improve treatment outcomes for children and adolescents with viraemia while taking ART. FUNDING: Fondation Botnar, Swiss National Science Foundation, and Gottfried and Julia Bangerter-Rhyner Foundation. TRANSLATIONS: For the Sesotho and Swahili translations of the abstract see Supplementary Materials section.