Details

Autor(en) / Beteiligte

• Boyer, Paul L
• Rehm, Catherine A
• Sneller, Michael C
• Mican, JoAnn
• Caplan, Margaret R
• Dewar, Robin
• Ferris, Andrea L
• Clark, Patrick
• Johnson, Adam
• Maldarelli, Frank
• Hughes, Stephen H

Titel

A Combination of Amino Acid Mutations Leads to Resistance to Multiple Nucleoside Analogs in Reverse Transcriptases from HIV-1 Subtypes B and C

Ist Teil von

• Antimicrobial agents and chemotherapy, 2022-01, Vol.66 (1), p.e0150021-e0150021

Ort / Verlag

United States: American Society for Microbiology

Erscheinungsjahr

2022

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Resistance to anti-HIV drugs has been a problem from the beginning of antiviral drug treatments. The recent expansion of combination antiretroviral therapy worldwide has led to an increase in resistance to antiretrovirals; understanding the mechanisms of resistance is increasingly important. In this study, we analyzed reverse transcriptase (RT) variants based on sequences derived from an individual who had low-level rebound viremia while undergoing therapy with abacavir, azidothymidine (AZT) (zidovudine), and (-)-l-2',3'-dideoxy-3'-thiacytidine (3TC) (lamivudine). The RT had mutations at positions 64, 67, 70, 184, and 219 and a threonine insertion after amino acid 69 in RT. The virus remained partially susceptible to the nucleoside RT inhibitor (NRTI) regimen. We show how these mutations affect the ability of NRTIs to inhibit DNA synthesis by RT. The presence of the inserted threonine reduced the susceptibility of the RT mutant to inhibition by tenofovir.