Intra-host HIV-1 Evolutionary Dynamics in Antiretroviral Therapy-Experienced People: A Systematic Review of Longitudinal Clinical Studies, Sarah Mirae Choi, UG '24 (F4573D0A)
The Joint United Nations Program on HIV/AIDS has aimed for 95% of people living with HIV (PLHIV) to have received their diagnosis, 95% of diagnosed PLHIV to have accessed treatment, and 95% of these PLHIV to have maintained viral suppression by 2025. We therefore expect the vast majority of PLHIV to be treatment-experienced in the near future. However, it remains unclear how the intrahost evolutionary trajectory of HIV-1 quasispecies is impacted by the initiation/presence of antiretroviral therapy (ART). By systematically reviewing published literature on HIV-1 intra-host evolution, this thesis aims to collate and explain seemingly disparate findings and identify which populations remain underrepresented in the literature. This is the first systematic review synthesizing qualitative findings from longitudinal studies examining HIV-1 treatment-experienced patients. Across the 65 included studies, key underrepresented populations were identified: PLHIV from African regions, women, and PLHIV infected with non-HIV-1 subtype B strains. The synthesis in this review offers important recommendations for future research. Firstly, future longitudinal studies should prioritize including more PLHIV from the aforementioned underrepresented groups. Secondly, more studies should examine how pre-treatment HIV RNA samples compare to post-treatment samples in patients who initiate ART during acute or chronic infection, as time between seroconversion and ART initiation may have important implications for subsequent intra-host evolution. Thirdly, patients experiencing periods of incomplete ART should be closely monitored for changes in divergence and/or diversity, as various included studies have noted accompanying risks of drug resistance and/or treatment failure in such patients.