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HIV Drug Resistance Profile in Clients Experiencing Treatment Failure After the Transition to a Dolutegravir-Based First-Line Antiretroviral Treatment Regimen in Mozambique

Abstract

Real-world data on HIV drug resistance (HIVDR) after transitioning to tenofovir disoproxil fumarate/lamivudine/dolutegravir (TLD) are limited. We assessed HIVDR rates and patterns in clients with virological failure (VF) after switching from an NNRTI-based regimen to TLD. A cross-sectional study was conducted in Gaza, Mozambique (August 2021-February 2022), including adults on first-line ART for ≥12 months who transitioned to TLD and had unsuppressed viral load (VL) ≥ 1000 copies/mL six months post-transition. After three adherence counseling sessions, participants with VF underwent genotyping for drug resistance mutations (DRMs) using the Stanford HIVdb Program. Of 717 participants (median age 39.2 years, 70.7% female), 217 (30.2%) had VF, 193 (88.9%) underwent genotyping, with 183 (94.8%) successfully genotyped. Intermediate-high dolutegravir (DTG) resistance was found in 19.6% (36/183). Unsuppressed VL before DTG transition was independently associated with VF (aOR: 2.14). Resistance patterns included 33.3% (12/36; 95% CI: 14.6-46.3) to all three TLD drugs, 55.6% (20/36; 95% CI: 39.3-71.9) to DTG and 3TC, and 11% (4/36; 95% CI: 0.8-21.3) to DTG only. Major drug resistance mutations to DTG included G118R (9.3%), R263K (6.6%), and Q148H/R/K (4.4%). This study highlights the need to consider virologic status before transitioning PLHIV to TLD and suggests that adherence counseling may not prevent resistance in those with unknown or prior VF.

References
1.
Kityo C, Mambule I, Musaazi J, Sokhela S, Mugerwa H, Ategeka G . Switch to long-acting cabotegravir and rilpivirine in virologically suppressed adults with HIV in Africa (CARES): week 48 results from a randomised, multicentre, open-label, non-inferiority trial. Lancet Infect Dis. 2024; 24(10):1083-1092. DOI: 10.1016/S1473-3099(24)00289-5. View

2.
Oliveira M, Ramalho D, Abreu C, Vubil A, Mabunda N, Ismael N . Genetic diversity and naturally polymorphisms in HIV type 1 integrase isolates from Maputo, Mozambique: implications for integrase inhibitors. AIDS Res Hum Retroviruses. 2012; 28(12):1788-92. PMC: 3505052. DOI: 10.1089/aid.2012.0058. View

3.
McCluskey S, Muyindike W, Nanfuka V, Omoding D, Komukama N, Barigye I . Population Effectiveness of Dolutegravir Implementation in Uganda: A Prospective Observational Cohort Study (DISCO), 48-Week Results. J Infect Dis. 2024; 230(3):e622-e630. PMC: 11420783. DOI: 10.1093/infdis/jiae260. View

4.
Hashempour A, Musavi Z, Moayedi J, Hasanshahi Z, Dehghani B, Ghasabi F . Transmitted Drug Resistance Against Integrase Strand Transfer Inhibitors in Iranian HIV-Infected Naïve Patients. Avicenna J Med Biotechnol. 2023; 15(3):203-206. PMC: 10395453. DOI: 10.18502/ajmb.v15i3.12931. View

5.
Murphy R, Bedesi P, Perumal N, Gosnell B, Hatlen T, Brijkumar J . Dolutegravir Resistance in African Programmatic Settings Among Patients With Failure of Dolutegravir-based ART. Open Forum Infect Dis. 2024; 11(7):ofae321. PMC: 11214099. DOI: 10.1093/ofid/ofae321. View