HIV-1 evolutionary dynamics under nonsuppressive antiretroviral therapy

Kemp, Steven A, Charles, Oscar J, Derache, Anne, Smidt, Werner, Martin, Darren P, Iwuji, Collins, Adamson, John, Govender, Katya, de Oliveira, Tulio, Dabis, Francois, Pillay, Deenan, Goldstein, Richard A and Gupta, Ravindra K (2022) HIV-1 evolutionary dynamics under nonsuppressive antiretroviral therapy. mBio. pp. 1-19. ISSN 2161-2129

[img] PDF - Published Version
Available under License Creative Commons Attribution.

Download (4MB)

Abstract

Prolonged virologic failure on 2nd-line protease inhibitor (PI)-based antiretroviral therapy (ART) without emergence of major protease mutations is well recognized and provides an opportunity to study within-host evolution in long-term viremic individuals. Using next-generation sequencing and in silico haplotype reconstruction, we analyzed whole-genome sequences from longitudinal plasma samples of eight chronically infected HIV-1-positive individuals failing 2nd-line regimens from the French National Agency for AIDS and Viral Hepatitis Research (ANRS) 12249 Treatment as Prevention (TasP) trial. On nonsuppressive ART, there were large fluctuations in synonymous and nonsynonymous variant frequencies despite stable viremia. Reconstructed haplotypes provided evidence for selective sweeps during periods of partial adherence, and viral haplotype competition, during periods of low drug exposure. Drug resistance mutations in reverse transcriptase (RT) were used as markers of viral haplotypes in the reservoir, and their distribution over time indicated recombination. We independently observed linkage disequilibrium decay, indicative of recombination. These data highlight dramatic changes in virus population structure that occur during stable viremia under nonsuppressive ART.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Global Health and Infection
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 20 May 2022 09:36
Last Modified: 20 May 2022 09:45
URI: http://sro.sussex.ac.uk/id/eprint/106009

View download statistics for this item

📧 Request an update