High Level of HIV Drug Resistance Informs Dolutegravir Roll-out and Optimized NRTI Backbone Strategy in Mozambique

Overview

Journal JAC Antimicrob Resist

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2021 Jul 5

PMID 34223118

Citations 5

Authors

V Carnimeo

I A Pulido Tarquino

S Fuentes

D Vaz

L Molfino

N Tamayo Antabak

R M Cuco

A Couto

S Lobo

J de Amaral Fidelis

J S Mulassua

I Ciglenecki

T Ellman

B Schramm

Affiliations

Soon will be listed here.

Abstract

Background: HIV drug resistance (HIV-DR) is rising in sub-Saharan Africa in both ART-naive and ART-experienced patients.

Objectives: To estimate the level of acquired DR (ADR) and pre-treatment DR (PDR) across selected urban and rural sites in Southern Africa, in Mozambique.

Methods: We conducted two cross-sectional surveys among adult HIV patients (October 2017-18) assessing ADR and PDR. In the (ADR) survey, those on NNRTI-based first-line ART for ≥6 months were recruited (three sites). In the PDR survey, those ART-naive or experienced with ≥3 months of treatment interruption prior were enrolled (eight sites).

Results: Among 1113 ADR survey participants 83% were receiving tenofovir (TDF)/lamivudine (3TC)/efavirenz (EFV). The median time on ART was 4.5 years (Maputo) and 3.2 years (Tete), 8.3% (95% CI 6.2%-10.6%, Maputo) and 15.5% (Tete) had a VL ≥ 1000 copies/mL, among whom 66% and 76.4% had NNRTI+NRTI resistance, and 52.8% and 66.7% had 3TC+TDF-DR. Among those on TDF regimens, 31.1% (Maputo) and 42.2% (Tete) were still TDF susceptible, whereas 24.4% and 11.5% had TDF+zidovudine (ZDV)-DR. Among those on ZDV regimens, 25% and 54.5% had TDF+ZDV-DR. The PDR survey included 735 participants: NNRTI-PDR was 16.8% (12.0-22.6) (Maputo) and 31.2% (26.2-36.6) (Tete), with a higher proportion (≥50%) among those previously on ART affected by PDR.

Conclusions: In Mozambique, viral failure was driven by NNRTI and NRTI resistance, with NRTI DR affecting backbone options. NNRTI-PDR levels surpassed the WHO 10% 'alert' threshold. Replacing NNRTI first-line drugs is urgent, as is frequent viral load monitoring and resistance surveillance. Changing NRTI backbones when switching to second-line regimens may need reconsideration.

Citing Articles

HIV-1 Antiretroviral Drug Resistance in Mozambique: A Systematic Review and Meta-Analysis.

Goncalves P, Mascarenhas P, Marcelino R, Mabunda N, Kroidl A, Buck W Viruses. 2025; 16(12.

PMID: 39772119 PMC: 11680126. DOI: 10.3390/v16121808.

Viral load suppression and HIV-1 drug resistance mutations in persons with HIV on TLD/TAFED in Zambia.

Luwaya E, Mwape L, Bwalya K, Siakabanze C, Hamooya B, Masenga S PLoS One. 2024; 19(9):e0308869.

PMID: 39241081 PMC: 11379217. DOI: 10.1371/journal.pone.0308869.

HIV-1 pretreatment and acquired antiretroviral drug resistance before tenofovir/ /lamivudine /dolutegravir (TLD) roll-out in Mozambique.

Ismael N, Gemusse H, Mahumane I, Laurindo O, Magul C, Baxter C BMC Infect Dis. 2024; 24(1):748.

PMID: 39075381 PMC: 11285440. DOI: 10.1186/s12879-024-09579-4.

Affordable drug resistance genotyping of HIV-1 reverse transcriptase, protease and integrase genes, for resource limited settings.

Manyana S, Pillay M, Gounder L, Khan A, Moodley P, Naidoo K AIDS Res Ther. 2023; 20(1):9.

PMID: 36759801 PMC: 9912687. DOI: 10.1186/s12981-023-00505-3.

Nevirapine hair and plasma concentrations and HIV-1 viral suppression among HIV infected ante-partum and post-partum women attended in a mother and child prevention program in Maputo city, Mozambique.

Cuco R, Loquiha O, Juga A, Couto A, Meggi B, Vubil A PLoS One. 2022; 17(2):e0261522.

PMID: 35143515 PMC: 8830619. DOI: 10.1371/journal.pone.0261522.

References

Pulido Tarquino I, Venables E, de Amaral Fidelis J, Giuliani R, Decroo T . "I take my pills every day, but then it goes up, goes down. I don't know what's going on": Perceptions of HIV virological failure in a rural context in Mozambique. A qualitative research study. PLoS One. 2019; 14(6):e0218364. PMC: 6576769. DOI: 10.1371/journal.pone.0218364. 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

Zhou Z, Wagar N, DeVos J, Rottinghaus E, Diallo K, Nguyen D . Optimization of a low cost and broadly sensitive genotyping assay for HIV-1 drug resistance surveillance and monitoring in resource-limited settings. PLoS One. 2011; 6(11):e28184. PMC: 3223235. DOI: 10.1371/journal.pone.0028184. View

Boender T, Kityo C, Boerma R, Hamers R, Ondoa P, Wellington M . Accumulation of HIV-1 drug resistance after continued virological failure on first-line ART in adults and children in sub-Saharan Africa. J Antimicrob Chemother. 2016; 71(10):2918-27. DOI: 10.1093/jac/dkw218. View

Gupta R, Gregson J, Parkin N, Haile-Selassie H, Tanuri A, Andrade Forero L . HIV-1 drug resistance before initiation or re-initiation of first-line antiretroviral therapy in low-income and middle-income countries: a systematic review and meta-regression analysis. Lancet Infect Dis. 2017; 18(3):346-355. PMC: 5835664. DOI: 10.1016/S1473-3099(17)30702-8. View

Ehrenkranz P, Baptiste S, Bygrave H, Ellman T, Doi N, Grimsrud A . The missed potential of CD4 and viral load testing to improve clinical outcomes for people living with HIV in lower-resource settings. PLoS Med. 2019; 16(5):e1002820. PMC: 6541248. DOI: 10.1371/journal.pmed.1002820. View

Jordan M, Penazzato M, Cournil A, Vubil A, Jani I, Hunt G . Human Immunodeficiency Virus (HIV) Drug Resistance in African Infants and Young Children Newly Diagnosed With HIV: A Multicountry Analysis. Clin Infect Dis. 2017; 65(12):2018-2025. DOI: 10.1093/cid/cix698. View

Sendagire H, Easterbrook P, Nankya I, Arts E, Thomas D, Reynolds S . The challenge of HIV-1 antiretroviral resistance in Africa in the era of HAART. AIDS Rev. 2009; 11(2):59-70. PMC: 3412282. View

Bila D, Young P, Merks H, Vubil A, Mahomed M, Augusto A . Evolution of primary HIV drug resistance in a subtype C dominated epidemic in Mozambique. PLoS One. 2013; 8(7):e68213. PMC: 3728366. DOI: 10.1371/journal.pone.0068213. View

10.

Shroufi A, Van Cutsem G, Cambiano V, Bansi-Matharu L, Duncan K, Murphy R . Simplifying switch to second-line antiretroviral therapy in sub Saharan Africa: predicted effect of using a single viral load to define efavirenz-based first-line failure. AIDS. 2019; 33(10):1635-1644. PMC: 6641111. DOI: 10.1097/QAD.0000000000002234. View

11.

Harris P, Taylor R, Thielke R, Payne J, Gonzalez N, Conde J . Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2008; 42(2):377-81. PMC: 2700030. DOI: 10.1016/j.jbi.2008.08.010. View

12.

De Luca A, Sidumo Z, Zanelli G, Magid N, Luhanga R, Brambilla D . Accumulation of HIV-1 drug resistance in patients on a standard thymidine analogue-based first line antiretroviral therapy after virological failure: implications for the activity of next-line regimens from a longitudinal study in Mozambique. BMC Infect Dis. 2017; 17(1):605. PMC: 5584020. DOI: 10.1186/s12879-017-2709-x. View

13.

Roberts T, Cohn J, Bonner K, Hargreaves S . Scale-up of Routine Viral Load Testing in Resource-Poor Settings: Current and Future Implementation Challenges. Clin Infect Dis. 2016; 62(8):1043-8. PMC: 4803106. DOI: 10.1093/cid/ciw001. View

14.

Swenson L, Min J, Woods C, Cai E, Li J, Montaner J . HIV drug resistance detected during low-level viraemia is associated with subsequent virologic failure. AIDS. 2014; 28(8):1125-34. PMC: 4278403. DOI: 10.1097/QAD.0000000000000203. View

15.

Bernal E, Gomez J, Jarrin I, Cano A, Munoz A, Alcaraz A . Low-Level Viremia Is Associated With Clinical Progression in HIV-Infected Patients Receiving Antiretroviral Treatment. J Acquir Immune Defic Syndr. 2018; 78(3):329-337. DOI: 10.1097/QAI.0000000000001678. View

16.

Ruperez M, Noguera-Julian M, Gonzalez R, Maculuve S, Bellido R, Vala A . HIV drug resistance patterns in pregnant women using next generation sequence in Mozambique. PLoS One. 2018; 13(5):e0196451. PMC: 5942837. DOI: 10.1371/journal.pone.0196451. View

17.

Inzaule S, Ondoa P, Peter T, Mugyenyi P, Stevens W, Wit T . Affordable HIV drug-resistance testing for monitoring of antiretroviral therapy in sub-Saharan Africa. Lancet Infect Dis. 2016; 16(11):e267-e275. DOI: 10.1016/S1473-3099(16)30118-9. View

18.

Vitoria M, Hill A, Ford N, Doherty M, Clayden P, Venter F . The transition to dolutegravir and other new antiretrovirals in low-income and middle-income countries: what are the issues?. AIDS. 2018; 32(12):1551-1561. DOI: 10.1097/QAD.0000000000001845. View

19.

Lafort Y, Couto A, Sunderbrink U, Hoek R, Shargie E, Zhao J . Validity of reported retention in antiretroviral therapy after roll-out to peripheral facilities in Mozambique: Results of a retrospective national cohort analysis. PLoS One. 2018; 13(6):e0198916. PMC: 6013210. DOI: 10.1371/journal.pone.0198916. View