High performance of integrase genotyping on diverse HIV-1 clades circulating in Cameroon: toward a successful transition to dolutegravir-based regimens in low and middle-income countries

Abstract

A successful transition to dolutegravir-based regimens in low and middle-income countries (LMICs) requires an integrase genotyping assay effective on diverse HIV-1 clades. We herein developed and validated an in-house integrase genotyping protocol on plasma samples from 195 HIV-infected patients in Cameroon. Median [IQR] viremia was 23,574 (518-109,235) copies/mL; 128/195 participants had ≥1000copies/mL (i.e., WHO-threshold for genotypic resistance testing in LMICs). A total of 18 viral clades were detected: 72(51.1%) CRF02_AG, 38(26.9%) pure subtypes and 31(22.0%) other recombinants. Following WHO-threshold (≥1000copies/ml), sequencing performance was 82.81%(106/128). Regarding viremia, performance was 85.00%(68/80) with ≥100,000copies/mL versus 76.67%(23/30) with 10,000 to 99,999copies/mL (P = 0.22); 83.33%(15/18) with 1,000 to 99,999copies/mL (P = 0.55); 73.68%(14/19) with 500 to 999copies/mL (P = 0.19); 50%(13/26) for 200 to 499copies/mL (P = 0.0005) and 36.36%(8/22) for <200copies/mL (P < 0.0001). The developed in-house integrase-genotyping is highly effective on both pure and recombinant viral clades, even at low-level viremia. This performance underscores its usefulness in monitoring integrase-resistance mutations and supporting the scale-up of dolutegravir-based regimens in LMICs.

Keywords: Cameroon; HIV-1; Integrase-genotyping; dolutegravir; viral clades.