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Host genomics of the HIV-1 reservoir size and its decay rate during suppressive antiretroviral treatment


Abstract

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 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- 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.

Abstract

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 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- 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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Virology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:18 August 2020
Deposited On:26 Oct 2020 18:13
Last Modified:19 Feb 2021 09:20
Publisher:Lippincott Williams & Wilkins
ISSN:1525-4135
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1097/QAI.0000000000002473
PubMed ID:32826560

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