Host genomics of the HIV-1 reservoir size and its decay rate during suppressive antiretroviral treatment. JAIDS
Thorball et al. aimed to assess host genetic factors associated with the HIV-1 reservoir size and its long-term dynamics in a cohort of 797 HIV-1 positive individuals on suppressive antiretroviral therapy (ART) for at least 5 years.
The authors measured total HIV-1 DNA in peripheral blood mononuclear cells from study participants, as a proxy for the reservoir size at 3 time points over a median of 5.4 years, and searched for associations between human genetic variation and 2 phenotypic readouts: the reservoir size at the first time point and its decay rate over the study period. They assessed the contribution of common genetic variants using genome-wide genotyping data from 797 patients with European ancestry enrolled in the Swiss HIV Cohort Study and searched for a potential impact of rare variants and exonic copy number variants using exome sequencing data generated in a subset of 194 study participants.
Based on their results, genome-wide and exome-wide analyses did not reveal any significant association with the size of the HIV-1 reservoir or its decay rate on suppressive antiretroviral treatment.
In conclusion, the study suggests that human individual germline genetic variation has little, if any, influence on the control of the HIV-1 viral reservoir size and its long-term dynamics. Complex, likely multifactorial biological processes govern HIV-1 viral persistence. Larger genomic studies, taking into account defined biological phenotypes and the differential biological importance of replication-competent and defective proviruses, will possibly clarify the role of common or rare genetic variants explaining small proportions of the variability of the phenotypes related to viral latency.