Patterns of HIV-1 Drug Resistance Observed Through Geospatial Analysis of Routine Diagnostic Testing in KwaZulu-Natal, South Africa

Viruses. 2024 Oct 19;16(10):1634. doi: 10.3390/v16101634.

Abstract

HIV-1 drug resistance (HIVDR) impedes treatment and control of HIV-1, especially in high-prevalence settings such as KwaZulu-Natal (KZN) province, South Africa. This study merged routine HIV-1 genotypic resistance test (GRT) data with Geographic Information Systems coordinates to assess patterns and geographic distribution of HIVDR in KZN, among ART-experienced adults with virological failure. We curated 3133 GRT records generated between 1 January 2018 and 30 June 2022, which includes the early phase of dolutegravir (DTG) rollout, of which 2735 (87.30%) had HIVDR. Of the 2735, major protease, nucleoside, and non-nucleoside reverse transcriptase inhibitor mutations were detected in 41.24%, 84.97% and 88.08% of GRTs, respectively. Additional genotyping of HIV-1 integrase for 41/3133 (1.31%) GRTs showed that 17/41 (41.46%) had integrase strand transfer inhibitor resistance. Notably, of 26 patients on DTG with integrase genotyping, 9 (34.62%) had DTG-associated resistance mutations. Dual- or triple-class resistance was observed in four of every five GRTs. The odds of HIVDR increased significantly with age, with ≥60 years having 5 times higher odds of HIVDR compared to 18-29 years (p = 0.001). We identified geospatial differences in the burden of HIVDR, providing proof of concept that this could be used for data-driven public health decision making. Ongoing real-time HIVDR surveillance is essential for evaluating the outcomes of the updated South African HIV treatment programme.

Keywords: HIV-1; KwaZulu-Natal; South Africa; dolutegravir; drug resistance; genotypic susceptibility scores; geospatial analysis.

MeSH terms

  • Adolescent
  • Adult
  • Anti-HIV Agents* / pharmacology
  • Anti-HIV Agents* / therapeutic use
  • Diagnostic Tests, Routine
  • Drug Resistance, Viral* / genetics
  • Female
  • Genotype*
  • HIV Infections* / drug therapy
  • HIV Infections* / epidemiology
  • HIV Infections* / virology
  • HIV-1* / drug effects
  • HIV-1* / genetics
  • Heterocyclic Compounds, 3-Ring / pharmacology
  • Heterocyclic Compounds, 3-Ring / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Oxazines
  • Piperazines
  • Pyridones
  • South Africa / epidemiology
  • Young Adult

Substances

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