Title : Assessing HIV-1 drug resistance in patients with virological failure amid the rollout of dolutegravir in hyperendemic KwaZulu-Natal, South Africa
Abstract:
Background: HIV drug resistance (HIVDR) remains a major threat to achieving sustainable viral suppression in patients on antiretroviral therapy (ART). In South Africa, since its rollout in December 2019, dolutegravir (DTG) has been the preferred ART backbone.
Methods: We curated HIVDR genotypic data obtained from the National Health Laboratory Service (NHLS) for ART-experienced patients with virological failure (i.e., consecutive viral loads ≥1,000 copies/mL) receiving HIV care at public-sector healthcare facilities in KwaZulu-Natal (KZN), South Africa. We estimated the levels of HIVDR from genotypes collected between January 2020 and June 2022, and assessed temporal trends in HIVDR across 11 districts of KZN following DTG-rollout in South Africa.
Results: Of the 2,380 genotypes curated, 2,049 (86.1% CI 84.6–87.5) had HIVDR mutations, with most resistance mutations occurring among adult females aged >19 years, (p=0.01). Protease inhibitor (PI)-specific mutations were present in one-third of genotypes, including 671 (28.2%) with additional resistance to nucleoside, and non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations. Only 39 genotypes had integrase resistance data, 9 (23.1%) of which had intermediate to high levels of resistance to DTG. Overall, compared with densely populated peri-urban and urban districts, rural districts had fewer HIVDR genotypes (369/2380, 15.5%) but more HIVDR (86.4% CI 82.5–89.8)
Conclusions: Six out of seven genotypes from patients with virologic failure had HIVDR mutations despite DTG-rollout, with persistent NNRTI resistance. Thus, while the introduction of DTG is expected to alleviate the HIVDR burden, a sub-population of people may not fully benefit from DTG-use due to multi-drug resistance, at which point PI-based ART may be warranted. There were higher proportions of HIVDR in rural districts and among adult women, highlighting regions and individuals needing priority HIV care. Overall, these findings urge the strengthening of HIV services in public healthcare systems to ensure sustainable DTG-use in first-line and subsequent ART regimens.
