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

Christian W Thorball, Alessandro Borghesi, Nadine Bachmann, Chantal Von Siebenthal, Valentina Vongrad, Teja Turk, Kathrin Neumann, Niko Beerenwinkel, Jasmina Bogojeska, Volker Roth, Yik Lim Kok, Sonali Parbhoo, Mario Wieser, Jürg Böni, Matthieu Perreau, Thomas Klimkait, Sabine Yerly, Manuel Battegay, Andri Rauch, Patrick Schmid, Enos Bernasconi, Matthias Cavassini, Roger D Kouyos, Huldrych F Günthard, Karin J Metzner, Jacques Fellay & Swiss HIV Cohort Study

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.

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.
   
citation Thorball C W, Borghesi A, Bachmann N, Von Siebenthal C, Vongrad V, Turk T, Neumann K, Beerenwinkel N, Bogojeska J, Roth V, Kok Y L, Parbhoo S, Wieser M, Böni J, Perreau M, Klimkait T, Yerly S, Battegay M, Rauch A, Schmid P, Bernasconi E, Cavassini M, Kouyos R D, Günthard H F, Metzner K J, Fellay J, Swiss HIV Cohort Study . Host Genomics of the HIV-1 Reservoir Size and Its Decay Rate During Suppressive Antiretroviral Treatment. J Acquir Immune Defic Syndr 2020; 85:517-524.
   
type journal paper/review (English)
date of publishing 01-12-2020
journal title J Acquir Immune Defic Syndr (85/4)
ISSN electronic 1944-7884
pages 517-524
PubMed 33136754
DOI 10.1097/QAI.0000000000002473