Fred Nalugoda | PubMed Health

PubMed2025

Patterns of HIV-1 viral load suppression and drug resistance during the dolutegravir transition: a population-based longitudinal study.

BACKGROUND: Data on the population-scale impact of dolutegravir (DTG)-based HIV regimens in sub-Saharan Africa are extremely limited. We used data from a surveillance cohort in southern Uganda to assess viral suppression and antiretroviral (ART) resistance over 10-years alongside DTG scale-up. METHODS: Consenting participants in the population-based Rakai Community Cohort Study between August 2011 and March 2023 aged 15-59 completed questionnaires and provided samples for HIV testing, viral load quantification, and viral deep-sequencing. We collected data on DTG-utilization at HIV care clinics. We estimated the prevalence of HIV suppression (<1,000 copies/mL) and ART resistance using robust Poisson regression. Bayesian logistic regression quantified associations between resistance and individual-level suppression across surveys. FINDINGS: Among 20,383 people living with HIV (PLHIV), suppression increased from 57.1% (95% confidence interval [CI]: 55.4%-58.8%) to 90.3% (95%CI: 89.2%-91.4%) between 2014 and 2022. By 2020 84.4% (95%CI: 83.7%-85.2%) and 64.6% (95%CI: 63.9%-65.3%) of men and women were on DTG regimens. Among treatment-experienced viremic PLHIV, overall resistance decreased from 51.1% (95%CI: 40.7%-64.1%, 2014) to 27.9% (95%CI: 21.3%-36.5%, 2022). Only two participants harbored intermediate/high-level DTG resistance, attributable to inQ148R, inE138K, and inG140A. Low-level INSTI resistance (inS153Y) was observed in 23/207 (7.5%) of viremic individuals, with putative evidence of transmission. By 2022, suppression was unrelated to prior history of NNRTI/NRTI resistance (risk ratios: 1.14, 95%HPD: 0.96-1.32 and 1.12, 95%HPD: 0.88 - 1.35). INTERPRETATION: Viral suppression increased during the DTG-transition with minimal emerging intermediate/high-level resistance. Falling resistance among treatment-experienced PLHIV underscores the role of ART adherence in reducing viremia. The emergence of inS153Y justifies continued genomic surveillance of ART resistance. FUNDING: National Institutes of Health and the Gates Foundation.

Journal Article↗

PubMed2024

Age and gender profiles of HIV infection burden and viraemia: novel metrics for HIV epidemic control in African populations with high antiretroviral therapy coverage.

INTRODUCTION: To prioritize and tailor interventions for ending AIDS by 2030 in Africa, it is important to characterize the population groups in which HIV viraemia is concentrating. METHODS: We analysed HIV testing and viral load data collected between 2013-2019 from the open, population-based Rakai Community Cohort Study (RCCS) in Uganda, to estimate HIV seroprevalence and population viral suppression over time by gender, one-year age bands and residence in inland and fishing communities. All estimates were standardized to the underlying source population using census data. We then assessed 95-95-95 targets in their ability to identify the populations in which viraemia concentrates. RESULTS: Following the implementation of Universal Test and Treat, the proportion of individuals with viraemia decreased from 4.9% (4.6%-5.3%) in 2013 to 1.9% (1.7%-2.2%) in 2019 in inland communities and from 19.1% (18.0%-20.4%) in 2013 to 4.7% (4.0%-5.5%) in 2019 in fishing communities. Viraemia did not concentrate in the age and gender groups furthest from achieving 95-95-95 targets. Instead, in both inland and fishing communities, women aged 25-29 and men aged 30-34 were the 5-year age groups that contributed most to population-level viraemia in 2019, despite these groups being close to or had already achieved 95-95-95 targets. CONCLUSIONS: The 95-95-95 targets provide a useful benchmark for monitoring progress towards HIV epidemic control, but do not contextualize underlying population structures and so may direct interventions towards groups that represent a marginal fraction of the population with viraemia.

Universal Test and Treat↗