Acquired HIV-1 drug resistance to reverse transcriptase and protease inhibitors among people failing antiretroviral therapy in Cameroon and implications for future treatment options

Abstract

HIV-1 drug resistance (HIVDR) surveillance among individuals failing antiretroviral therapy (ART) is essential to selecting optimal ART-combinations for use in a public health approach in low-middle-income countries (LMICs) where routine HIVDR-testing remains limited. This study describes patterns of acquired drug resistance (ADR) and potentially active drugs for subsequent ART regimens in individuals failing treatment in Cameroon. We conducted a cross-sectional, laboratory-based sentinel study among ART-failing individuals from October 2022 through April 2023 at the "Chantal Biya" International Reference Centre, Yaoundé-Cameroon. Individual samples with confirmed virological failure were sequenced in HIV-1 protease and reverse-transcriptase genes using Sanger sequencing and analysed using Stanford HIVdatabase.v.9.4. Overall, 203 individuals were enrolled, median [IQR] age 37 [16-47] years with 58.1% (118/203) being female. Median [IQR] duration on ART was 10 [6.9-13.3] years, with majority failing second-line (78.7%; 160/203). HIVDR rate was 85.3% (29/34) and 88.1% (140/160) in those failing first-line and second-line therapy respectively (p = 0.7). NNRTI, NRTI and PI/r resistance in individuals failing first-line ART was 85.3% (9/34), 82.4% (28/34) and 2.9% (1/34) respectively. In second-line failure, NNRTI, NRTI and PI/r resistance was 86.8% (138/160), 84.9% (135/160) and 47.17% (75/160) respectively. NRTI-NNRTI dual-class-resistance was 82.4% (28/34) after first-line and 84.3% (134/160) after second-line (p = 0.842), while triple-class-resistance was 2.9% (1/34) after first-line and 45.3% (72/160) after second-line (p < 0.0001). After first-line, TDF and AZT maintained potential efficacy in respectively 53.4% (18/34) and 46.7% (16/34) of individuals, while 46.7% (16/34) had cross-resistance to second-generation NNRTI. After second-line failure, 95.6% (153/160) maintained DRV/r efficacy, as compared to 67.3% for ATV/r (p < 0.0002), 73.9% for LPV/r (p < 0.0002), and 34.7% (56/160) for RPV/DOR. Among ART-failing individuals in Cameroon, levels of ADR are high with significant levels of cross-resistance to second-generation NNRTI, hence potentially jeopardizing the use of long-acting cabotegravir/rilpivirine. Furthermore, HIVDR testing could be considered from first-line failure in such settings, but chiefly following second-line failure wherein triple-class-resistance is common and calls for novel antiretrovirals in similar LMICs.