Dolutegravir-Based Therapy is Essential in Achieving HIV Epidemic Control in Low- and Middle-Income Countries: Real-Life Evidence from a Large Clinical Cohort in Cameroon

BACKGROUND: HIV treatment has significantly improved with the introduction of potent antiretroviral therapy (ART), particularly dolutegravir (DTG)-based regimens. With suboptimal adherence reported in resource-limited settings (RLS), real-word evidence on DTG-effectiveness within ART clinics is limited. This study assessed virological response, drug resistance profiling and HIV-1 diversity among ART recipients at the Yaoundé Central Hospital (YCH), Cameroon. METHODS: A facility-based study was conducted at YCH from March-2023 to February-2025. HIV plasma viral load (PVL) was measured by RT-PCR. Viral suppression (VS) was defined as PVL<1,000copies/mL. Genotypic resistance testing (GRT) was performed for participants with PVL³1,000copies/mL. Drug resistance mutations (DRMs) were interpreted using Stanford HIVdb v9.8 and statistics were performed with significance at p<0.05. RESULTS: Among 6,364 participants enrolled (median-age: 50 [IQR:42–59] years; 71% women), 76% (4,811/6364) were on DTG-based regimens. Median ART-duration was 13 [IQR:9.03–17.4] years, including 3.4 [IQR:3–5] years of DTG-exposure in the DTG-based sub-group. Overall, 93.2% (5,932/6,364) participants achieved VS in 2025; 94% among DTG-based versus 91% among DTG-sparing regimens (OR=1.66; p=0.000002). Interestingly, VS was higher with age ³50years (aOR=1.44; p<0.001), DTG-based ART (aOR=1.65; p<0.0001) and DTG-exposure ³3.4years (aOR=1.29; p=0.044). Between 2021-2025 specifically, VS remained consistently high among participants; with those on DTG-based showing significantly higher and more durable VS compared to those on DTG-sparing therapies (relative risk of failure >1 for DTG-sparing throughout). Furthermore, from those virally unsuppressed in 2025, 9% (39/432) were lost-to-follow-up, 22% (94/432) were transfer-out to other health facilities and 65% (232/432) re-suppressed after enhanced adherence counselling; leaving us with 17 participants eligible for GRT (PVL³1000copies/mL). GRT was successful for 70.5% (12/17) and DRMs detected in 83% (10/12), including major DRMs to protease inhibitors (17%), to nucleoside reverse transcriptase inhibitors (75%) and to non-nucleoside reverse transcriptase inhibitors (83%). CRF02_AG (75%) was the prevailing HIV-1 group M clade, followed by A3, D, and CRF18_cpx (each 8.3%). CONCLUSION: These real-life data reveal viral suppression rates closer to the epidemic control (95%) among DTG-based recipients, especially with older age and DTG-exposure over three years. Considering the broad HIV diversity observed, these findings are essential for modelling the long-term effectiveness of DTG in RLS and beyond. Trial registration: Ethical Clearance Number 2023/022045/CEIRSH/ESS/BC