Temporal Trends in HIV-1 Genetic Diversity in Cameroon: A Sequence Database Analysis from 1990–2023

Abstract

Abstract Background and Aim HIV exhibits extensive genetic diversity with important consequences for viral-fitness, diagnostic-performance, therapeutic-response, and the emergence of drug resistance. In the context of major changes in antiretroviral therapy-(ART) availability, we investigated long-term-HIV-1-clade dynamics in Cameroon over more than three decades to inform projections of viral evolution toward 2030. Methodology A total of 12,230 HIV sequences generated between 1990-and-2023 were analyzed and grouped into three periods reflecting ART rollout:1990–2000-(minimal ART availability), 2001–2011-(reverse-transcriptase-inhibitor-era), and 2012–2023-(high-coverage-highly-potent ART era). Temporal-trends in clade-proportions were assessed using Cochran–Armitage-trend test, logistic regression models were fitted to evaluate the association between calendar year and the probability of observing specific HIV-1 clades. Forecasting analyses were done with generalized-additive-models to estimate future clade proportions up to 2030. Model fit was evaluated using Akaike-Information-Criterion (AIC), to confirm robustness of the models and Shannon entropy measured the genetic variability of the Pol gene across the time-point intervals. Results HIV-1 overwhelmingly predominated throughout the study period-(99.98%), with HIV-2 remaining rare-(0.02%). Within HIV-1, Group-M was consistently dominant and increased significantly over time, while Groups O, N, and P declined markedly. Circulating-recombinant forms-(CRFs), particularly CRF02_AG-related lineages, expanded substantially and became the major drivers of viral-diversity, whereas unclassified-recombinants declined. Weighted analysis confirmed that these temporal trends were not artifacts of uneven sequencing efforts, addressing a key limitation commonly associated with sequence database studies. Forecasting analyses suggest that by 2030, HIV-1 group M is likely to remain the predominant circulating lineage in Cameroon, although the persistence of rare clades cannot be excluded given the limitations of available sequence data. Furthermore, Entropy-analyses showed slight differences in genetic variability over the years, suggesting overall stability of the Pol region despite decades of viral evolution as compared to Env gene. Conclusion These findings underscore the central role of recombination in shaping HIV-1-evolution in Cameroon and highlight the necessity of continuous genomic-surveillance and next-generation-therapeutic and preventive strategies to support progress toward HIV-elimination by 2030 in genetically diverse settings.