HIV-1 re-suppression on a first-line regimen despite the presence of phenotypic drug resistance

Adriaan E. Basson, Salome Charalambous, Christopher J. Hoffmann, Lynn Morris

Research output: Contribution to journalArticle

Abstract

We have previously reported on HIV-1 infected patients who fail anti-retroviral therapy but manage to re-suppress without a regimen change despite harbouring major drug resistance mutations. Here we explore phenotypic drug resistance in such patients in order to better understand this phenomenon. Patients (n = 71) failing a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen, but who subsequently re-suppressed on the same regimen, were assessed for HIV-1 genotypic drug resistance through Sanger sequencing. A subset (n = 23) of these samples, as well as genotypically matched samples from patients who did not re-suppress (n = 19), were further assessed for phenotypic drug resistance in an in vitro single cycle assay. Half of the patients (n = 36/71, 51%) harboured genotypic drug resistance, with M184V (n = 18/36, 50%) and K103N (n = 16/36, 44%) being the most prevalent mutations. No significant difference in the median time to re-suppression (31-39 weeks) were observed for either group (p = 0.41). However, re-suppressors with mutant virus rebounded significantly earlier than those with wild-type virus (16 vs. 33 weeks; p = 0.014). Similar phenotypic drug resistance profiles were observed between patients who re-suppressed and patients who failed to re-suppress. While most remained susceptible to stavudine (d4T) and zidovudine (AZT), both groups showed a reduced susceptibility to 3TC and NNRTIs. HIV- 1 infected patients on an NNRTI-based regimen can achieve viral re-suppression on the same regimen despite harbouring viruses with genotypic and phenotypic drug resistance. However, re-suppression was less durable in those with resistance, reinforcing the importance of appropriate regimen choices, ongoing viral load monitoring and adherence counselling.

Original languageEnglish (US)
Article numbere0234937
JournalPloS one
Volume15
Issue number6
DOIs
StatePublished - Jun 2020

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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