TY - JOUR
T1 - Host Genomics of the HIV-1 Reservoir Size and Its Decay Rate During Suppressive Antiretroviral Treatment
AU - Swiss HIV Cohort Study
AU - Thorball, Christian W.
AU - Borghesi, Alessandro
AU - Bachmann, Nadine
AU - Von Siebenthal, Chantal
AU - Vongrad, Valentina
AU - Turk, Teja
AU - Neumann, Kathrin
AU - Beerenwinkel, Niko
AU - Bogojeska, Jasmina
AU - Roth, Volker
AU - Kok, Yik Lim
AU - Parbhoo, Sonali
AU - Wieser, Mario
AU - Böni, Jürg
AU - Perreau, Matthieu
AU - Klimkait, Thomas
AU - Yerly, Sabine
AU - Battegay, Manuel
AU - Rauch, Andri
AU - Schmid, Patrick
AU - Bernasconi, Enos
AU - Cavassini, Matthias
AU - Kouyos, Roger D.
AU - Günthard, Huldrych F.
AU - Metzner, Karin J.
AU - Fellay, Jacques
N1 - Copyright:
This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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. 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, 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 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. 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-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. 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.
AB - 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. 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, 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 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. 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-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. 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.
UR - http://www.scopus.com/inward/record.url?scp=85095403411&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85095403411&partnerID=8YFLogxK
U2 - 10.1097/QAI.0000000000002473
DO - 10.1097/QAI.0000000000002473
M3 - Article
C2 - 33136754
AN - SCOPUS:85095403411
VL - 85
SP - 517
EP - 524
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
SN - 1525-4135
IS - 4
ER -