Abstract
BackgroundHuman immunodeficiency virus (HIV) increasing molecular diversity and emergence of drug resistant mutants remain a major concern in China. Enfuvirtide (ENF/T-20) is the first 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 China is limited. The objective was to identify molecular diversity and ENF resistance patterns of HIV-1 in southern China, using envelope (env) gp41 sequences and bioinformatics tools, which may help optimize antiretroviral therapy. MethodsFrom November 2018 to January 2019, 439 blood plasma samples from ENF-naïve 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). ResultsThe main subtypes were circulating recombinant form (CRF) 01_AE (30.6 %) and CRF07_BC (48.7 %). CRF55_01B had been the fourth subtype in the study, and many rare CRFs were observed. Notably, CRF02_AG and CRF_BF strains typically found in Africa and US respectively were identified amongst Chinese patients. Known DRMs were detected in 27.5 % (109/396) of ENF treatment-naïve patients. One major DRM (L44 M), many secondary DRMs (including N126 K, E137 K, S138A), and lots of polymorphisms were found in the study, which have been proved to elevate resistance to ENF. ConclusionsHIV-1 molecular diversity was observed in the study, which indicating that HIV-1 variability is becoming increasingly complex in southern China. A diverse set of primary DRMs discovered in this study described the serious threat to ART, which reminds us the urgent need of timely surveillance of HIV-1 viral diversity and drug resistance in China.
Highlights
Human immunodeficiency virus type one (HIV-1) presents high genetic diversity, and is suppressed by antiretroviral therapy (ART), but may acquire many drug resistance-associated mutations (DRMs)
The distribution of HIV-1 subtypes among the three cities in the study demonstrated that the HIV-1 isolates in Shenzhen were more variable than Chongqing and Wuhan (P < 0.01), and the proportions of CRF07_BC and CRF08_BC in Chongqing were higher than the other two cities (P < 0.01)
Molecular characterization of the HIV-1 isolates circulating within the HIV-1 patients in southern China revealed the most prevalent subtypes were CRF01_AE and CRF07_BC, while CRF08_BC and subtype B showed the lower prevalence in comparison to the national report in China in 2006 [27]
Summary
Human immunodeficiency virus type one (HIV-1) presents high genetic diversity, and is suppressed by antiretroviral therapy (ART), but may acquire many drug resistance-associated mutations (DRMs). Molecular epidemiological studies demonstrated that CRF07_BC, CRF01_AE and CRF08_BC were the dominant subtypes among the population of southern China, with identification of drug-resistant strains and novel unique recombinant forms (URFs) [5,6,7]. Human immunodeficiency virus (HIV) increasing molecular diversity and emergence of drug resistant mutants remain a major concern in Southern China, enfuvirtide (ENF/T-20) is the first entry inhibitor used in patients failing highly active antiretroviral therapy (HAART). 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) gp sequences and bioinformatics tools, which may help optimize ART
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