Drug Resistance-Associated Mutations in Antiretroviral Treatment-Experienced Patients in Kuwait

Abstract

Objectives: To investigate the prevalence of nonpolymorphic resistance-associated mutations (RAM) in HIV-1 patients on first-line antiretroviral therapy in Kuwait. Subjects and Methods: Total RNA was isolated from plasma samples of 42 patients who received a first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen. HIV-1 protease and reverse transcriptase genetic regions were then amplified by nested reverse transcription-polymerase chain reaction and directly sequenced. The HIV-1 subtype was identified using the Bayesian phylogenetic method, and RAM were identified using the Stanford University genotypic resistance interpretation algorithm. Results: The HIV-1 viral load at sampling ranged from < 20 to 8.25 × 10⁴ copies/ml. CRF01_AE, C, and B were the most predominant HIV-1 subtypes. Nonpolymorphic mutations associated with resistance to antiretroviral drugs were detected in 11 (26.2%) of the 42 patients; 5 (11.9%) patients had mutations associated with a high-level resistance to nucleoside reverse transcriptase inhibitors (NRTI), 4 (9.5%) patients had mutations associated with resistance to NNRTI, 1 (2.4%) patient had mutations associated with resistance to both NRTI and NNRTI, and 1 (2.4%) patient had mutations potentially associated with low-level resistance to both protease inhibitors and NNRTI. All patients with RAM had a detectable plasma HIV-1 RNA level. Conclusion: Our results indicate the development of RAM during an NNRTI-based regimen and highlight the importance of considering other regimens to avoid treatment failure.

Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting

“…In our previous studies, we reported the detection of major mutations conferring resistance to nucleoside and non-nucleoside reverse transcriptase inhibitors (NNRTIs) in 12.5% of 64 ART-naive patients, and about 30% of 64 treatment-experienced patients. 17 Major non-polymorphic mutations that confer resistance to InSTIs were not detected in 53 InSTI-naïve patients. 18 Given the scarce information on HIV-1 drug resistance in real clinical settings, especially in the Arabian Gulf region, we aimed in this report to characterize the patterns of mutations detected among patients who did not achieve viral suppression following 48 weeks of treatment with InSTI-based regimen.…”