Investigation of Antiretroviral Therapy (ART) use and drug resistance characteristics in HIV-positive patients

Abstract

In recent years, the global increase in drug resistance rates against antiretroviral therapy (ART) regimens has underscored the importance of incorporating HIV drug resistance testing into routine clinical practice and its critical role in treatment success. The aim of this study was to determine HIV drug resistance and the associated genetic mutations in 278 treatment-naive HIV-1 infected patients followed at our clinic. This single center retrospective study included treatment-naive HIV-1 infected individuals followed at our institution. The protease and reverse transcriptase regions of the HIV-1 pol gene were analyzed by Sanger sequencing. HIV-1 subtype analysis was performed using the REGA HIV-1 Subtyping Tool version 3.0, and drug resistance mutations (DRMs) were interpreted using the Stanford HIV Drug Resistance Database (HIVdb v9.7). Of the 278 treatment-naive HIV-1–infected patients, 240 (86.3%) were male and 38 (13.7%) were female. The median age was 42 years (Q1–Q3: 31–51), with no significant difference between sexes ( p = 0.432). The median CD4 cell count was 381 cells/mm³ (Q1–Q3: 280–468). Subtype B was the predominant HIV-1 subtype (34.0%), followed by subtypes A (32.4%) and F (16.2%). Protease inhibitor (PI) associated mutations were detected in 51 patients (18.3%), including 45 (16.2%) major DRMs. Nucleoside reverse transcriptase inhibitor (NRTI) associated mutations were detected in 37 patients (13.3%), including 7 (2.5%) major DRMs. Non-nucleoside reverse transcriptase inhibitor (NNRTI) associated mutations were detected in 66 patients (23.7%), most of which represented polymorphic and/or accessory variants; clinically relevant NNRTI DRMs were identified in only 6 patients (2.2%). The most frequently detected mutations were M46L among PI-associated mutations, S68G among NRTI-associated mutations, M184V among major NRTI DRMs, and E138G/A and K103N among NNRTI-associated mutations. Susceptibility to guideline-recommended first-line agents remained high, with rates of 99.6% for TDF, 98.2% for FTC/3TC, and 98.5% for DOR, whereas susceptibility rates for alternative agents were 83.8% for ATV/r, 99.6% for DRV/r, and 78.4% for RPV. Although clinically relevant PI DRMs were more frequent than previously reported, the prevalence of clinically relevant NRTI and NNRTI DRMs remained low. These findings support the continued effectiveness of current guideline-recommended first-line ART regimens and highlight the importance of baseline genotypic resistance testing.