Host Genomics of the HIV-1 Reservoir Size and Its Decay Rate During Suppressive Antiretroviral Treatment.
Journal
Journal of acquired immune deficiency syndromes (1999)
ISSN: 1944-7884
Titre abrégé: J Acquir Immune Defic Syndr
Pays: United States
ID NLM: 100892005
Informations de publication
Date de publication:
01 12 2020
01 12 2020
Historique:
entrez:
2
11
2020
pubmed:
3
11
2020
medline:
7
4
2021
Statut:
ppublish
Résumé
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. 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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 33136754
doi: 10.1097/QAI.0000000000002473
pii: 00126334-202012010-00020
doi:
Substances chimiques
Anti-HIV Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
517-524Références
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