Monitoring of virological response and acquired HIV-1 drug resistance among patients initiating antiretroviral therapy in the Centre Region of Cameroon.

Introduction: despite the success of antiretroviral therapy (ART), the emergence of HIV drug resistance (HIVDR) remains a major threat in sub-Saharan Africa, where therapeutic options remain limited. With the goal of supporting ART response, we sought to monitor viral load (VL) response and acquired HIVDR emergence among patients initiating ART in the Cameroonian setting. Methods: a facility-based cohort study was conducted from March 2016 to May 2021 in urban (Yaoundé) and rural (Obala) settings in the Centre Region of Cameroon. Included were recently diagnosed HIV individuals initiating ART at the level of the health facilities. VL was measured at three different time points. For those with unsuppressed viremia (>1000 copies/mL), genotyping for HIVDR was performed in the protease, reverse-transcriptase, and integrase gene regions, and interpreted using HIVdb.v9.1. Data were analyzed with p<0.05 considered significant. Time-to-event analysis (Kaplan-Meier and Cox regression) was used to identify determinants of virological failure. Results: overall, 87 newly diagnosed participants (50.6% from urban and 49.4% from rural) were enrolled. Median (interquartile range, IQR) age was 42 (34.0-50.5) years, sex ratio (F/M) was 3/2, and all participants initiated treatment with non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART regimen. At initiation, median VL was 34,000 (13,963-122,000) copies/mL; at T1 (~3 years after initiation), median VL dropped to 9,800 (4,700-30,500) copies/mL, and 17.2% (15/87) switched to protease inhibitor-based ART. At the end of the study (T2), 58.6% (51/87) had achieved undetectable VL (<40copies/mL), 3.4% had VL between 40-999 copies/mL, and 37.9% VL >1000 copies/mL. The proportion with virological failure was 9.1% (4/44) in the urban setting versus 67.4% (29/43) in the rural setting. Time-to-event analysis revealed that patients in the rural setting had a 4.6-fold higher risk of virological failure (hazard ratio (HR) = 4.60, 95% CI: 2.29-9.27). Among those with unsuppressed VL, overall rate of HIVDR was 62.5% (20/32), driven by the mutations: M184V (31.25%) for NRTI, K103N (18.75%) for NNRTI and M46I (9.30%) for PI/r, and 0% major resistance mutations to integrase strand transfer inhibitors (INSTI), without any significant disparity between urban and rural. Conclusion: viral load monitoring reveals poor ART response in rural settings, which prompts the need for improving access to ART. Among those with unsuppressed VL, the burden and patterns of HIVDR are similar in both settings, likely due to the wide use of NNRTI-based ART. Viral susceptibility to INSTIs supports a possible switch to dolutegravir-based ART for optimal response.