A Whole-Genome Association Study of Major Determinants for Host Control of HIV-1

TLDR

Effective HIV‑1 control varies among individuals, and understanding this variation is key to developing new treatments. The study used a whole‑genome association approach to identify polymorphisms explaining nearly 15 % of variation in viral load set‑point. Polymorphisms near HLA‑B*5701, HLA‑C, and an RNA polymerase I subunit were linked to viral load set‑point and disease progression, underscoring the role of human genetics in HIV control.

Abstract

Understanding why some people establish and maintain effective control of HIV-1 and others do not is a priority in the effort to develop new treatments for HIV/AIDS. Using a whole-genome association strategy, we identified polymorphisms that explain nearly 15% of the variation among individuals in viral load during the asymptomatic set-point period of infection. One of these is found within an endogenous retroviral element and is associated with major histocompatibility allele human leukocyte antigen ( HLA )– B*5701 , whereas a second is located near the HLA-C gene. An additional analysis of the time to HIV disease progression implicated two genes, one of which encodes an RNA polymerase I subunit. These findings emphasize the importance of studying human genetic variation as a guide to combating infectious agents.