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. 2021 Oct 16;18(1):74.
doi: 10.1186/s12981-021-00393-5.

Acquired HIV drug resistance and virologic monitoring in a HIV hyper-endemic setting in KwaZulu-Natal Province, South Africa

Benjamin Chimukangara  1   2   3 , Richard J Lessells  4 , Lavanya Singh  4 , Indra Grigalionyte  5 , Nonhlanhla Yende-Zuma  5   6 , Rochelle Adams  5 , Halima Dawood  5   7 , Linda Dlamini  8 , Sibonisile Buthelezi  9 , Sheldon Chetty  9 , Karidia Diallo  10 , Wayne A Duffus  10 , Mary Mogashoa  10 , Melissa B Hagen  10 , Jennifer Giandhari  4 , Tulio de Oliveira  5   4 , Pravi Moodley  11 , Nesri Padayatchi  5 , Kogieleum Naidoo  5   6
Affiliations

Acquired HIV drug resistance and virologic monitoring in a HIV hyper-endemic setting in KwaZulu-Natal Province, South Africa

Benjamin Chimukangara et al. AIDS Res Ther. .

Abstract

Background: Introduction of tenofovir (TDF) plus lamivudine (3TC) and dolutegravir (DTG) in first- and second-line HIV treatment regimens in South Africa warrants characterization of acquired HIV-1 drug resistance (ADR) mutations that could impact DTG-based antiretroviral therapy (ART). In this study, we sought to determine prevalence of ADR mutations and their potential impact on susceptibility to drugs used in combination with DTG among HIV-positive adults (≥ 18 years) accessing routine care at a selected ART facility in KwaZulu-Natal, South Africa.

Methods: We enrolled adult participants in a cross-sectional study between May and September 2019. Eligible participants had a most recent documented viral load (VL) ≥ 1000 copies/mL after at least 6 months on ART. We genotyped HIV-1 reverse transcriptase and protease genes by Sanger sequencing and assessed ADR. We characterized the effect of ADR mutations on the predicted susceptibility to drugs used in combination with DTG.

Results: From 143 participants enrolled, we obtained sequence data for 115 (80%), and 92.2% (95% CI 85.7-96.4) had ADR. The proportion with ADR was similar for participants on first-line ART (65/70, 92.9%, 95% CI 84.1-97.6) and those on second-line ART (40/44, 90.9%, 95% CI 78.3-97.5), and was present for the single participant on third-line ART. Approximately 89% (62/70) of those on first-line ART had dual class NRTI and NNRTI resistance and only six (13.6%) of those on second-line ART had major PI mutations. Most participants (82%) with first-line viraemia maintained susceptibility to Zidovudine (AZT), and the majority of them had lost susceptibility to TDF (71%) and 3TC (84%). Approximately two in every five TDF-treated individuals had thymidine analogue mutations (TAMs).

Conclusions: Susceptibility to AZT among most participants with first-line viraemia suggests that a new second-line regimen of AZT + 3TC + DTG could be effective. However, atypical occurrence of TAMs in TDF-treated individuals suggests a less effective AZT + 3TC + DTG regimen in a subpopulation of patients. As most patients with first-line viraemia had at least low-level resistance to TDF and 3TC, identifying viraemia before switch to TDF + 3TC + DTG is important to avoid DTG functional monotherapy. These findings highlight a need for close monitoring of outcomes on new standardized treatment regimens.

Keywords: Acquired drug resistance; Antiretroviral treatment; HIV-1; KwaZulu-Natal; Viraemia.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Participant and sample flow from enrolment to analysis in the acquired HIV drug resistance study in KwaZulu-Natal (KZN) province, South Africa
Fig. 2
Fig. 2
Predicted susceptibility of virus isolates from participants with viraemia receiving a tenofovir, emtricitabine and efavirenz combination regimen
See this image and copyright information in PMC

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