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

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2024 Oct 26

PMID 39459966

Authors

Lilishia Gounder

Aabida Khan

Justen Manasa

Richard Lessells

Andrew Tomita

Melendhran Pillay

Sontaga C Manyana

Subitha Govender

Kerri-Lee Francois

Pravi Moodley

Nokukhanya Msomi

Kerusha Govender

Raveen Parboosing

Sikhulile Moyo

Kogieleum Naidoo

Benjamin Chimukangara

Affiliations

Soon will be listed here.

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 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 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 ( = 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.

References

Li J, Stella N, Choudhary M, Javed A, Rodriguez K, Ribaudo H . Impact of pre-existing drug resistance on risk of virological failure in South Africa. J Antimicrob Chemother. 2021; 76(6):1558-1563. PMC: 8599859. DOI: 10.1093/jac/dkab062. View

Peterson M, Gandhi N, Clennon J, Nelson K, Morris N, Ismail N . Extensively drug-resistant tuberculosis 'hotspots' and sociodemographic associations in Durban, South Africa. Int J Tuberc Lung Dis. 2019; 23(6):720-727. PMC: 6641858. DOI: 10.5588/ijtld.18.0575. View

Loosli T, Hossmann S, Ingle S, Okhai H, Kusejko K, Mouton J . HIV-1 drug resistance in people on dolutegravir-based antiretroviral therapy: a collaborative cohort analysis. Lancet HIV. 2023; 10(11):e733-e741. PMC: 10913014. DOI: 10.1016/S2352-3018(23)00228-X. View

Sy K, Leavitt S, De Vos M, Dolby T, Bor J, Horsburgh Jr C . Spatial heterogeneity of extensively drug resistant-tuberculosis in Western Cape Province, South Africa. Sci Rep. 2022; 12(1):10844. PMC: 9237070. DOI: 10.1038/s41598-022-14581-4. View

McLaren Z, Ardington C, Leibbrandt M . Distance decay and persistent health care disparities in South Africa. BMC Health Serv Res. 2014; 14:541. PMC: 4236491. DOI: 10.1186/s12913-014-0541-1. View

Kim H, Tanser F, Tomita A, Vandormael A, Cuadros D . Beyond HIV prevalence: identifying people living with HIV within underserved areas in South Africa. BMJ Glob Health. 2021; 6(4). PMC: 8061852. DOI: 10.1136/bmjgh-2020-004089. View

Siedner M, Moorhouse M, Simmons B, de Oliveira T, Lessells R, Giandhari J . Reduced efficacy of HIV-1 integrase inhibitors in patients with drug resistance mutations in reverse transcriptase. Nat Commun. 2020; 11(1):5922. PMC: 7708638. DOI: 10.1038/s41467-020-19801-x. View

Chimukangara B, Lessells R, Rhee S, Giandhari J, Kharsany A, Naidoo K . Trends in Pretreatment HIV-1 Drug Resistance in Antiretroviral Therapy-naive Adults in South Africa, 2000-2016: A Pooled Sequence Analysis. EClinicalMedicine. 2019; 9:26-34. PMC: 6510720. DOI: 10.1016/j.eclinm.2019.03.006. View

Gounder L, Tomita A, Lessells R, Moodley S, Francois K, Khan A . Geospatial and temporal mapping of detectable HIV-1 viral loads amid dolutegravir rollout in KwaZulu-Natal, South Africa. PLOS Glob Public Health. 2024; 4(5):e0003224. PMC: 11132473. DOI: 10.1371/journal.pgph.0003224. View

10.

Hermans L, Steegen K, Ter Heine R, Schuurman R, Tempelman H, Moraba R . Drug level testing as a strategy to determine eligibility for drug resistance testing after failure of ART: a retrospective analysis of South African adult patients on second-line ART. J Int AIDS Soc. 2020; 23(6):e25501. PMC: 7282495. DOI: 10.1002/jia2.25501. View

11.

Van Laethem K, Schrooten Y, Covens K, Dekeersmaeker N, De Munter P, Van Wijngaerden E . A genotypic assay for the amplification and sequencing of integrase from diverse HIV-1 group M subtypes. J Virol Methods. 2008; 153(2):176-81. DOI: 10.1016/j.jviromet.2008.07.008. View

12.

Chimukangara B, Lessells R, Sartorius B, Gounder L, Manyana S, Pillay M . HIV-1 drug resistance in adults and adolescents on protease inhibitor-based antiretroviral therapy in KwaZulu-Natal Province, South Africa. J Glob Antimicrob Resist. 2021; 29:468-475. DOI: 10.1016/j.jgar.2021.10.023. View

13.

Buchanan A, Bekker A, Chandasana H, DeMasi R, Lulic Z, Ernest T . Advancing research and development of anti-infectives for children with a focus on antiretroviral therapy: A clinical development perspective. Int J Antimicrob Agents. 2024; 64(4):107306. DOI: 10.1016/j.ijantimicag.2024.107306. View

14.

Brijkumar J, Edwards J, Johnson B, Ordonez C, Sunpath H, Lee M . Comparing effectiveness of first-line antiretroviral therapy between peri-urban and rural clinics in KwaZulu-Natal, South Africa. HIV Med. 2022; 23(7):727-737. PMC: 9353676. DOI: 10.1111/hiv.13231. View

15.

Tambuyzer L, Vingerhoets J, Azijn H, Daems B, Nijs S, de Bethune M . Characterization of genotypic and phenotypic changes in HIV-1-infected patients with virologic failure on an etravirine-containing regimen in the DUET-1 and DUET-2 clinical studies. AIDS Res Hum Retroviruses. 2010; 26(11):1197-205. DOI: 10.1089/aid.2009.0302. View

16.

Chu C, Tao K, Kouamou V, Avalos A, Scott J, Grant P . Prevalence of Emergent Dolutegravir Resistance Mutations in People Living with HIV: A Rapid Scoping Review. Viruses. 2024; 16(3). PMC: 10975848. DOI: 10.3390/v16030399. View

17.

Wensing A, Calvez V, Ceccherini-Silberstein F, Charpentier C, Gunthard H, Paredes R . 2022 update of the drug resistance mutations in HIV-1. Top Antivir Med. 2022; 30(4):559-574. PMC: 9681141. View

18.

Gonzalez-Serna A, Glas A, Brumme C, Poon A, Nohpal De La Rosa A, Mudrikova T . Genotypic susceptibility score (GSS) and CD4+ T cell recovery in HIV-1 patients with suppressed viral load. J Antimicrob Chemother. 2016; 72(2):496-503. DOI: 10.1093/jac/dkw455. View

19.

Gregson J, Kaleebu P, Marconi V, van Vuuren C, Ndembi N, Hamers R . Occult HIV-1 drug resistance to thymidine analogues following failure of first-line tenofovir combined with a cytosine analogue and nevirapine or efavirenz in sub Saharan Africa: a retrospective multi-centre cohort study. Lancet Infect Dis. 2016; 17(3):296-304. PMC: 5421555. DOI: 10.1016/S1473-3099(16)30469-8. View

20.

Crowell T, Danboise B, Parikh A, Esber A, Dear N, Coakley P . Pretreatment and Acquired Antiretroviral Drug Resistance Among Persons Living With HIV in Four African Countries. Clin Infect Dis. 2020; 73(7):e2311-e2322. PMC: 8492117. DOI: 10.1093/cid/ciaa1161. View