Since the discovery of a cure has remained elusive, the development of a vaccine is likely to be the most effective strategy to curb the spread of the HIV/AIDS. CD8+ T cells play an important role in controlling HIV-1 replication, and they may present a key component of an effective HIV-1 vaccine. Under CD8+ T cell pressure, viral escape mutations are frequently selected and some result in significant viral fitness costs. While substantial replication costs of several immune escape mutations in the HIV-1 Gag have been demonstrated, less is known about the replication consequences of mutations in other HIV-1 proteins. Pol (comprised of protease, reverse transcriptase [RT] and integrase), is a conserved and immunogenic protein that is essential for viral replication, but the impact of mutations in this protein on virus replication capacity has not been adequately explored. Achieng’s PhD research project involved the utilisation of patient-derived RT-integrase sequences to explore the relationships between immune-driven sequence variation in RT-integrase, viral fitness, and markers of disease progression in HIV-1 subtype C infection. This study may inform which epitopes to include and which to avoid in vaccines that aim to limit immune escape through focussing on vulnerable regions of HIV-1.