Abstract
BackgroundThere is increasing evidence that HIV-1 genetic diversity can have an impact on drug resistance. The aim of this study is to investigate the epidemiological situation of CRF65_cpx and the impact of natural polymorphisms of this variant on genotypic resistance.MethodsWe used the BLAST search program followed by phylogenetic analysis to identify additional CRF65_cpx pol sequences from the Los Alamos HIV Sequence Database. Maximum likelihood phylogeny was estimated to clarify the epidemiological relationship of CRF65_cpx strains. Genotypic resistance was determined by submitting sequences to the Stanford HIV Drug Resistance Database.ResultsA total of 32 CRF65_cpx pol sequences were obtained. The CRF65_cpx strains were detected in seven provinces with large geographic distance. Yunnan CRF65_cpx sequences were mainly derived from a heterosexual risk group, whereas the CRF65_cpx sequences in other provinces were almost exclusively derived from an MSM population. With one exception of V179E, the other 31 strains harbored V179D mutation. The combination of V179D and K103R, conferring intermediate resistance to EFV and NVP, was detected in seven treatment-naive MSM patients.ConclusionsThis study confirmed the expansion CRF65_cpx in China. Furthermore, we found the natural presence of the V179D and K103R/V179D mutations associated with resistance to NNRTIs in HIV-1 CRF65_cpx. Our findings highlight the contribution of polymorphic mutations to drug resistance and underscore the challenges in treating patients harboring CRF65_cpx strains.
Highlights
There is increasing evidence that HIV-1 genetic diversity can have an impact on drug resistance
The pol region is routinely sequenced in the clinical context of genotypic drug resistance testing, and a large body of pol sequences are deposited in the Los Alamos HIV Sequence Database
We may be able to identify more CRF65_cpx sequences from the database to investigate its expansion. It seems that combination antiretroviral therapy (ART) is effective against all HIV-1 viral subtypes, there is increasing evidence that HIV-1 genetic diversity can have an impact on drug resistance
Summary
There is increasing evidence that HIV-1 genetic diversity can have an impact on drug resistance. The aim of this study is to investigate the epidemiological situation of CRF65_cpx and the impact of natural polymorphisms of this variant on genotypic resistance. We may be able to identify more CRF65_cpx sequences from the database to investigate its expansion It seems that combination antiretroviral therapy (ART) is effective against all HIV-1 viral subtypes, there is increasing evidence that HIV-1 genetic diversity can have an impact on drug resistance. The natural presence of drug resistance mutations in some viruses is already being observed. Most of the HIV-1 O group viruses are considered to be naturally resistant to nonnucleoside reverse transcriptase inhibitors (NNRTIs) due to the presence of the Y181C mutation [7]. Zhou et al reported that CRF01_AE subtype-related resistance to fostemsavir, an attachment inhibitor, appeared to be associated with the natural presence of substitutions S375H and M475I [8]
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