Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains.
Adult
Drug Resistance, Viral
/ genetics
Female
Genotype
HIV Infections
/ drug therapy
HIV-1
/ classification
Homosexuality, Male
Humans
Likelihood Functions
Male
Middle Aged
Mutation
Phylogeny
Reverse Transcriptase Inhibitors
/ therapeutic use
pol Gene Products, Human Immunodeficiency Virus
/ classification
CRF65_cpx
Drug resistance
HIV
V179D
Journal
BMC infectious diseases
ISSN: 1471-2334
Titre abrégé: BMC Infect Dis
Pays: England
ID NLM: 100968551
Informations de publication
Date de publication:
28 Apr 2020
28 Apr 2020
Historique:
received:
12
05
2019
accepted:
31
03
2020
entrez:
30
4
2020
pubmed:
30
4
2020
medline:
23
6
2020
Statut:
epublish
Résumé
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 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. A 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. This 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.
Sections du résumé
BACKGROUND
BACKGROUND
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.
METHODS
METHODS
We 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.
RESULTS
RESULTS
A 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.
CONCLUSIONS
CONCLUSIONS
This 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.
Identifiants
pubmed: 32345262
doi: 10.1186/s12879-020-05007-5
pii: 10.1186/s12879-020-05007-5
pmc: PMC7189696
doi:
Substances chimiques
Reverse Transcriptase Inhibitors
0
pol Gene Products, Human Immunodeficiency Virus
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
313Subventions
Organisme : NSFC
ID : 81773493
Organisme : NSFC
ID : 81273137
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