High rates of transmitted NNRTI resistance among persons with acute HIV infection in Malawi: implications for first-line dolutegravir scale-up

AIDS Res Ther. 2019 Feb 22;16(1):5. doi: 10.1186/s12981-019-0220-8.

Abstract

High rates of non-nucleoside reverse transcriptase inhibitors (NNRTI) resistance was a key consideration in the WHO policies transitioning first-line regimens to include integrase inhibitors (dolutegravir [DTG]). However, recent data suggests a relationship between DTG and neural tube defects among women exposed during conception, giving providers and policymakers pause regarding the planned regimen changes. We examined HIV drug resistance among a cohort of 46 acutely infected persons in Malawi. Our data demonstrates high levels of transmitted resistance, 11% using standard resistance surveillance mutations and 20% when additional NNRTI polymorphisms that may affect treatment response are included. High resistance rates in this treatment-naïve patient population reinforces the critical nature of DTG-based options in the context of public-health driven treatment programs.

Keywords: Acute HIV infection; Antiretroviral resistance; Dolutegravir; Malawi.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Cohort Studies
  • Drug Resistance, Viral*
  • Female
  • HIV Infections / epidemiology*
  • HIV Infections / transmission*
  • HIV Integrase Inhibitors / therapeutic use*
  • HIV-1 / drug effects
  • HIV-1 / genetics
  • Heterocyclic Compounds, 3-Ring / therapeutic use*
  • Humans
  • Malawi / epidemiology
  • Male
  • Middle Aged
  • Oxazines
  • Piperazines
  • Polymorphism, Genetic
  • Pyridones
  • Young Adult

Substances

  • Anti-HIV Agents
  • HIV Integrase Inhibitors
  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Pyridones
  • dolutegravir