Host Genomics of the HIV-1 Reservoir Size and Its Decay Rate During Suppressive Antiretroviral Treatment

BACKGROUND:The primary hurdle for the eradication of HIV-1 is the establishment of a latent viral reservoir early after primary infection. Here we investigated the potential influence of human genetic variation on the HIV-1 reservoir size and its decay rate during suppressive antiretroviral treatment (ART). SETTING:Genome-wide association study and exome sequencing study to look for host genetic determinants of HIV-1 reservoir measurements in patients enrolled in the Swiss HIV Cohort Study (SHCS), a nation-wide prospective observational study. METHODS:We measured total HIV-1 DNA in peripheral blood mononuclear cells from study participants, as a proxy for the reservoir size, at three time points over a median of 5.4 years, and searched for associations between human genetic variation and two phenotypic readoutsthe reservoir size at the first time point and its decay rate over the study period. We 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. RESULTS:Genome- and exome-wide analyses did not reveal any significant association with the size of the HIV-1 reservoir or its decay rate on suppressive ART. CONCLUSIONS:Our results point to a limited influence of human genetics on the size of the HIV-1 reservoir and its long-term dynamics in successfully treated individuals.