HIV-1 gp41 genetic diversity and enfuvirtide resistance-associated mutations among enfuvirtide-naïve patients in southern China

Abstract

Background: Human immunode ciency virus (HIV) increasing molecular diversity and emergence of drug resistant mutants remain a major concern in Southern China, enfuvirtide (ENF/T-20) is the rst entry inhibitor used in patients failing highly active antiretroviral therapy (HAART). However, data on HIV-1 gp41genetic diversity and primary ENF resistance-associated mutations among treatment-naïve patients in southern China is limited. The objective was to identify molecular diversity and ENF resistance patterns of HIV-1 in southern China, using envelop (env) gp41 sequences and bioinformatics tools, which may help optimize ART. Methods: From December 2018 to January 2019, 439 blood plasma samples from ENF-naïve HIV-1 patients were collected from Shenzhen, Wuhan and Chongqing, of which, 396 HIV env regions were sequenced and subtyped, and were performed the analysis of drug resistance-associated mutations (DRMs). Results: The main subtypes were circulating recombinant form (CRF) 01_AE (30.6%) and CRF07_BC (48.7%), CRF55_01B had been the fourth subtype in our work, many rare CRFs were observed. Notably, CRF02_AG and CRF_BF strains typically found in Africa and US respectively were identi ed amongst Chinese HIV-1 patients. Known DRMs were detected in 27.5% (109/396) of ENF treatment-naïve patients. One major DRM (L44M), many secondary DRMs including (N126K, E137K, S138A) and lots of polymorphisms were found in the study, which have been proved to elevate resistance to ENF. Conclusion: HIV-1 molecular diversity among people in southern China observed in the work indicates that HIV-1 variability is becoming increasingly complex in the south of China. A diverse set of primary DRMs discovered in this study described the serious threat to ART, which remind us the urgent need of timely surveillance of HIV-1 viral diversity and drug resistance in China.

Research Progress in the Epidemiology of HIV/AIDS in China

“…HIVDR or mutations to PIs and other antiretroviral drugs (ARV) were also emerging. Yang et al investigated the prevalence of integrase strand transfer inhibitors (INSTI)-associated resistance of HIV-1 strains in Henan Province during 2018-2020 (40). The prevalence of INSTI resistance was 1.2% overall, 0.63% for ART-naive patients, 2.05% for ART-treated patients with 14.63% for INSTI-treated and 0.76% for INSTI-naive patients.…”

“…The prevalence of INSTI resistance was 1.2% overall, 0.63% for ART-naive patients, 2.05% for ART-treated patients with 14.63% for INSTI-treated and 0.76% for INSTI-naive patients. In a study of HIV-1 gp41 genetic diversity and enfuvirtide (ENF/T-20) drug resistance-associated mutations (DRMs) among enfuvirtide-naive patients in southern China, known DRMs were detected in 27.5% of ENF treatment-naive patients, which have been proved to elevate resistance to ENF ( 41 ). Undoubtedly, HIVDR or DRMs will continue to evolve in an increasing trend which warrants enhanced surveillance and monitoring.…”

HIV Transmembrane Glycoprotein Conserved Domains and Genetic Markers Across HIV-1 and HIV-2 Variants

“…Thus, no natural major resistance mutations to T-20 were observed. The L44M change found in group P consensus sequence, previously associated with 1.8-fold resistance to T-20 in vitro (Mink et al, 2005), was previously found in T-20 naïve subjects from China (Chang et al, 2021), maybe reflecting a resistance transmission during primoinfection. New HIV-1 fusion inhibitors are under development (Luque and Camarasa, 2021) and previous studies showed that optimized T-20 derivates could have been effective inhibitors of infection for multiple HIV-1 variants (Chen et al, 2019).…”

HIV and Drug-Resistant Subtypes

“…The major polymorphisms were R46K/M/Q, E137K, and S138A. R46K/M/Q and S138A were predominant in subtype CRF07_BC, and E137K was prevalent in subtype B [ 121 ].…”