AI Summary
There is currently no cure for HIV, and it remains a major issue in low-income countries. Viral load and various factors contribute to HIV progression and transmission. Genetic factors and viral adaptation play a role in viral load variability. Studies have shown viral escape mutations from HLA class I alleles.
INTRODUCTIONNo cure for HIV has been ascertained in the 40 years since its discovery, and it remains a major public health concern that disproportionately affects people living in low-income countries (1). HIV disease progression is variable among untreated individuals and their viral load (VL), measured as HIV RNA copies/mL of plasma, is a predictor of disease progression (2–5) and transmission potential (6–9). Several factors contribute to an individual’s VL during infection including their environment, gender/sex, use of antiretroviral treatment (ART), attributes of the infecting virus, co-morbidities (including co-infections), and host genetics (2–4, 10, 11). Host genetic studies, primarily in populations of European ancestry, have consistently shown associations between variation in HLA and CCR5 with VL, accounting for up to 25% of VL variability in people not receiving ART (4, 12). In addition to host genetics, HIV sequence variation contributes ~30% to variability in VL (4, 5, 11, 12).A key component among individuals with untreated HIV infection is within-host viral evolution, where the virus adapts to its environment to maximize replication and transmission potential (13, 14). The best evidence for viral adaptation to host genetic variation comes from numerous studies identifying viral escape mutations from HLA class I alleles (13, 15–19). For example, HLAB*51 restricts an epitope in reverse transcriptase (RT) which selects for the I135X escape mutation in ~96% of HLAB*51 carriers and interferes with CD8+ T-cell recognition (13, 18). Importantly, HLAB*51 was protective against HIV disease progression prior to 1997 in Japanese populations where the allele frequency is