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. ### Competing Interest Statement MKG, LCW report grants from the National Institutes of Health during the conduct of this study. ABr, MM report an EPSRC PhD studentship during the conduct of this study. OR acknowledges grants from the Bill and Melinda Gates Foundation (OPP1175094 to C.Fraser., OPP1084362 to D. Pillay), the Engineering and Physical Sciences Research Council (EP/X038440/1), and the Moderna Charitable Foundation during the conduct of this study. This arrangement has been reviewed and approved by the Johns Hopkins University in accordance with its conflict-of-interest policies. ### Funding Statement This study was supported by the National Institute of Allergy and Infectious Diseases [U01AI075115 to RHG, R01AI087409 to RHG, U01AI100031 to RHG, ZIAAI001040 to TCQ, R01AI43333 to LWC]; the National Institute of Mental Health [F31MH095649 to Dr Jennifer Wagman, R01MH099733 to Ned Sacktor and MJW, R01MH107275 to LWC]; the Division of Intramural Research of the National Institute for Allergy and Infectious Diseases [TCQ, OL, SJR], NIAID [K01AA024068 to Dr Jennifer Wagman]; the Johns Hopkins University Center for AIDS Research [2P30AI094189 to Dr Richard Chaisson]; the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention [NU2GGH000817 to RHSP]; the Engineering and Physical Sciences Research Council through the EPSRC Centre for Doctoral Training in Modern Statistics and Statistical Machine Learning at Imperial and Oxford [EP/S023151/1 to Prof Axel Gandy]. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was independently reviewed and approved by the Ugandan Virus Research Institute, Research and Ethics Committee, protocol GC/127/13/01/16; the Ugandan National Council for Science and Technology; and the Western Institutional Review Board, protocol 200313317. All study participants provided written informed consent at baseline and follow-up visits using institutional review board approved forms. This project was reviewed in accordance with CDC human research protection procedures and was determined to be research, but CDC investigators did not interact with human subjects or have access to identifiable data or specimens for research purposes. RCCS participants received 10,000UGX (approximately 2.50USD) in compensation for their time and costs to participate in each survey I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data necessary to reproduce the analyses are available on Zenodo (https://doi.org/10.5281/zenodo.10955672) as open access dataset under the CC-BY-4.0 license. Code to reproduce all analyses is freely available on GitHub version 1.1.2 under the CC-BY-4.0 license at the repository (https://github.com/MLGlobalHealth/longi\_viral\_loads).