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

Abstract

Objective 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-naïve HIV-1–infected patients followed at our clinic. Methods This single-center retrospective study evaluated treatment-naïve HIV-1–infected individuals followed at our institution. Prior to ART initiation, whole blood samples collected in EDTA tubes were sent to the National HIV/AIDS Confirmation Center and Viral Hepatitis Reference Laboratory of the General Directorate of Public Health, Ministry of Health of Türkiye. Viral RNA extraction was performed, and the HIV-1 pol region was amplified using reverse transcription polymerase chain reaction (RT-PCR). Amplified products were examined by agarose gel electrophoresis and subsequently sequenced using the Sanger sequencing method on an ABI 3500 XL platform (Applied Biosystems, USA). The resulting FASTA sequences were aligned using Unipro Ugene v50 software, and consensus sequences for the protease and reverse transcriptase (RT) regions were generated. Viral subtype determination was performed using the Rega HIV-1 Subtyping Tool (v3). Drug resistance mutations (DRMs) were classified using the Stanford University HIV Drug Resistance Database (HIVdb v9.7), and resistance rates and mutation profiles were determined for protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs), and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Results Of the 278 treatment-naïve HIV-1–infected patients included in the study, 240 (86.3%) were male and 38 (13.7%) were female. The mean age was 41.8 ± 12.5 years, with no significant age difference between sexes (males: 41.5 ± 12.5; females: 43.4 ± 12.5; p = 0.397). Resistance-associated mutations (RAMs) were detected in 154 patients (55.4%). After excluding mutations that did not affect susceptibility to any antiretroviral agent, clinically relevant DRMs conferring resistance to at least one drug class were identified in 123 patients (44.2%).When DRM frequencies were evaluated in the entire cohort (n = 278), PI-associated mutations were detected in 51 patients (18.3%), NRTI-associated mutations in 14 patients (5.03%), and NNRTI-associated mutations in 63 patients (22.7%).After exclusion of polymorphic mutations in the NNRTI group, NNRTI resistance-associated mutations were identified in only nine patients (3.23%). The most frequently observed mutations were M46L for PIs, revertant-type T215D/N/S for NRTIs, and E138G/A and K103N for NNRTIs. Conclusions According to our findings, susceptibility rates of agents recommended for first-line therapy were 99.6% for TDF, 98.2% for FTC and 3TC, and 98.5% for DOR, whereas susceptibility rates for alternative treatment options were 83.8% for ATV, 99.6% for DRV, and 78.4% for RPV. Comparison of the observed DRM rates with the literature demonstrated that PI resistance was higher than reported global estimates, while NRTI and NNRTI resistance rates were consistent with international data. Antiretroviral drug resistance is well recognized as a key determinant of ART failure. Accordingly, prioritizing agents with a high genetic barrier in first-line therapy is essential for achieving sustained viral suppression and long-term treatment success.