mbio.00269-22.pdf (4.28 MB)
HIV-1 evolutionary dynamics under nonsuppressive antiretroviral therapy
journal contribution
posted on 2023-06-10, 03:37 authored by Steven A Kemp, Oscar J Charles, Anne Derache, Werner Smidt, Darren P Martin, Collins IwujiCollins Iwuji, John Adamson, Katya Govender, Tulio de Oliveira, Francois Dabis, Deenan Pillay, Richard A Goldstein, Ravindra K GuptaProlonged 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.
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- Published
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- Published version
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mBioISSN
2161-2129Publisher
American Society for MicrobiologyExternal DOI
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1-19Department affiliated with
- Global Health and Infection Publications
Full text available
- Yes
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- Yes
Legacy Posted Date
2022-05-20First Open Access (FOA) Date
2022-05-20First Compliant Deposit (FCD) Date
2022-05-20Usage metrics
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