HIV-1 genotypic patterns in antiretroviral-naïve and treated patients in the integrase inhibitor era in Morocco

HIV-1 drug resistance remains a critical challenge for long-term treatment effectiveness, particularly in settings characterized by diverse viral subtypes and evolving treatment histories. We investigated the prevalence, patterns, and molecular distribution of transmitted and acquired HIV-1 drug-resistance mutations in a Moroccan cohort. A cross-sectional molecular study was performed on HIV-1–infected individuals monitored at the CVMIT in Rabat from 2024 to 2025. Demographic, clinical, and virological data were collected retrospectively from medical records. The HIV-1 pol gene was amplified and sequenced. Drug-resistance mutations were interpreted using the Stanford HIVdb v9.8 algorithm, and resistance profiles were examined by drug class, resistance level, treatment history, and viral subtype. Major surveillance drug-resistance mutations were detected in 3 of 38 ART-naïve individuals (7.9%), indicating a low but measurable burden of transmitted resistance. These mutations were limited to protease inhibitor- and non-nucleoside reverse transcriptase inhibitor-associated substitutions, with no major transmitted resistance detected in nucleoside reverse transcriptase inhibitors or integrase inhibitors. Among ART-experienced patients, 11 of 26 individuals (42.3%) harbored at least one major resistance mutation. Acquired resistance was dominated by NNRTI mutations, led by K103N/S (19.2%), Y188L/H, and V106I/L (15.4%) each, followed by NRTI mutations including M184V/I (19.2%), D67N, and K70R/E (15.4%) each. Integrase inhibitor resistance was detected in three treated individuals (11.5%), involving R263K/T, Q148K, and N155H. No major protease inhibitor resistance was identified among treated patients. CRF02_AG accounted for the majority of major resistance mutations across drug classes. This study provides a detailed overview of HIV-1 DRMs in Morocco, revealing persistent NNRTI and NRTI resistance within a CRF02_AG-dominant epidemic and the emergence of INSTI mutations under DTG pressure. These findings emphasize the urgency of nationwide genotypic surveillance to guide ART management and preserve treatment efficacy.