SARS-CoV-2 Evolution in an HIV-Endemic Setting: A Genomic Epidemiology Study from Botswana.

Background: HIV infection can affect SARS-CoV-2 infection dynamics through prolonged viral replication and altered immune responses, but population-level genomic evidence from HIV-endemic settings is limited. Botswana, a country with high HIV prevalence and an established genomic surveillance infrastructure, provides an important setting to examine how host immune variation influences viral evolution during the Omicron period. Methods: We conducted a population-based genomic epidemiology study in the Greater Gaborone District between June 2022 and November 2024. Among 404 SARS-CoV-2 positive samples, 387 yielded high-quality genomes (Ct < 35). Phylogenetic trees were reconstructed using IQ-TREE, time-calibrated with TreeTime, and visualized in Nextstrain to illustrate lineage turnover and clustering patterns. Participant metadata, including HIV status and vaccination history, were summarized descriptively and incorporated into phylogenetic visualizations to annotate sequences by HIV status. Results: Six successive Omicron sublineage waves (BA.4/BA.5, BQ/FN, XBB, BA.2.86, KP, and XEC.9) were detected, consistent with repeated viral introductions rather than sustained local diversification. Sequences from HIV-positive and HIV-negative individuals were broadly interspersed throughout the phylogeny, indicating no population-level separation by HIV status. However, small dyads of HIV-positive hosts appeared within BA, JN, and KP sublineages. Interpretation: In a highly treated and vaccinated population, HIV infection did not fundamentally alter SARS-CoV-2 evolutionary trajectories at the population level. However, subtle clustering among HIV-positive hosts suggests possible host-specific effects, underscoring the importance of continued genomic surveillance integrating host immunologic and clinical data to detect early signals of viral adaptation.