Archived rilpivirine-associated resistance mutations among ART-naive and virologically suppressed people living with HIV-1 subtype C in Botswana: implications for cabotegravir/rilpivirine use

J Antimicrob Chemother. 2023 Oct 3;78(10):2489-2495. doi: 10.1093/jac/dkad258.

Abstract

Objectives: Pre-existing rilpivirine resistance-associated mutations (RVP-RAMs) have been found to predict HIV-1 virological failure in those switching to long-acting injectable cabotegravir/rilpivirine. We here evaluated the prevalence of archived RPV-RAMs in a cohort of people living with HIV (PWH).

Methods: We analysed near full-length HIV-1 pol sequences from proviral DNA for the presence of RPV-RAMs, which were defined according to the 2022 IAS-USA drug resistance mutation list and Stanford HIV drug resistance database.

Results: RPV-RAMs were identified in 757/5805 sequences, giving a prevalence of 13.0% (95% CI 12%-13.9%). Amongst the ART-naive group, 137/1281 (10.7%, 95% CI 9.1%-12.5%) had at least one RPV-RAM. Of the 4524 PWH with viral suppression on ART (VL <400 copies/mL), 620 (13.7%, 95% CI 12.7%-14.7%) had at least one RPV-RAM. E138A was the most prevalent RPV-RAM in the ART-naive group (7.9%) and the ART-suppressed group (9.3%). The rest of the mutations observed (L100I, K101E, E138G, E138K, E138Q, Y181C, H221Y, M230L, A98G, V179D, G190A, G190E and M230I) were below a prevalence of 1%.

Conclusions: RPV-RAMs were present in 10.7% of ART-naive and 13.7% of ART-suppressed PWH in Botswana. The most common RPV-RAM in both groups was E138A. Since individuals with the E138A mutation may be more likely to fail cabotegravir/rilpivirine, monitoring RPV-RAMs will be crucial for effective cabotegravir/rilpivirine implementation in this setting.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-HIV Agents* / pharmacology
  • Anti-HIV Agents* / therapeutic use
  • Anti-Retroviral Agents / therapeutic use
  • Botswana / epidemiology
  • Drug Resistance, Viral / genetics
  • Genotype
  • HIV Infections*
  • HIV Seropositivity* / drug therapy
  • HIV-1* / genetics
  • Humans
  • Mutation
  • Nitriles / pharmacology
  • Pyrimidines / pharmacology
  • Rilpivirine / pharmacology
  • Rilpivirine / therapeutic use

Substances

  • Rilpivirine
  • Anti-HIV Agents
  • cabotegravir
  • Nitriles
  • Pyrimidines
  • Anti-Retroviral Agents