Screening for and Verification of Novel Mutations Associated with Drug Resistance in the HIV Type 1subtype B′ in China

Li, Hanping; Geng, Qing-mao; Guo, Wei; Zhuang, Daomin; Lin, Li; Liu, Yongjian; Bao, Zhenmin; Liu, Siyang; Li, Jingyun

doi:10.1371/journal.pone.0047119

Cited by 3 publications

(1 citation statement)

References 34 publications

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“…11,12 Studies of HIV-1 RT genotype and phenotype patterns in ARV-naive and treatment failure patients in China are increasing but are still limited. 13,14 Although limited information on drug resistance in the newly emerged CRF08_BC has been obtained from treatment-naive patients, 15 there is still no published information on drug resistance mutation patterns after ARV exposure. In this study, we selected drugresistant variants of CRF08_BC by in vitro passage in peripheral blood mononuclear cells (PBMCs) with escalating concentrations of NVP, EFV, and 3TC, respectively.…”

Section: Introductionmentioning

confidence: 99%

In VitroSelection of HIV-1 CRF08_BC Variants Resistant to Reverse Transcriptase Inhibitors

Zhang

et al. 2015

AIDS Research and Human Retroviruses

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Human immunodeficiency virus type 1 (HIV-1) circulating recombinant form 08_BC (CRF08_BC), carrying the recombinant reverse transcriptase (RT) gene from subtypes B and C, has recently become highly prevalent in Southern China. As the number of patients increases, it is important to characterize the drug resistance mutations of CRF08_BC, especially against widely used antiretrovirals. In this study, clinically isolated virus (2007CNGX-HK), confirmed to be CRF08_BC with its sequence deposited in GenBank (KF312642), was propagated in human peripheral blood mononuclear cells (PBMCs) with increasing concentrations of nevirapine (NVP), efavirenz (EFV), or lamivudine (3TC). Three different resistance patterns led by initial mutations of Y181C, E138G, and Y188C were detected after the selection with NVP. Initial mutations, in combination with other previously reported substitutions (K20R, D67N, V90I, K101R/E, V106I/A, V108I, F116L, E138R, A139V, V189I, G190A, D218E, E203K, H221Y, F227L, N348I, and T369I) or novel mutations (V8I, S134N, C162Y, L228I, Y232H, E396G, and D404N), developed during NVP selection. EFV-associated variations contained two initial mutations (L100I and Y188C) and three other mutations (V106L, F116Y, and A139V). Phenotypic analyses showed that E138R, Y181C, and G190A contributed high-level resistance to NVP, while L100I and V106L significantly reduced virus susceptibility to EFV. Y188C was 20-fold less sensitive to both NVP and EFV. As expected, M184I alone, or with V90I or D67N, decreased 3TC susceptibility by over 1,000-fold. Although the mutation profile obtained in culture may be different from the patients, these results may still provide useful information to monitor and optimize the antiretroviral regimens.

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Section: Introductionmentioning

confidence: 99%

In VitroSelection of HIV-1 CRF08_BC Variants Resistant to Reverse Transcriptase Inhibitors

Zhang

et al. 2015

AIDS Research and Human Retroviruses

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Prevalence and patterns of drug-resistance mutations among HIV-1 patients infected with CRF07_BC strains in Sichuan province, China

Zhou

Yuan³

et al. 2014

Virol. Sin.

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Little information is available on the prevalence of drug-resistance mutations in patients harboring the human immunodeficiency virus type 1 (HIV-1) circulating recombinant form (CRF)07_BC variant in Sichuan, China. This study examined 375 plasma samples from patients with HIV-1 who were infected with the CRF07_BC strain, including 104 drug-naive participants and 271 in whom antiretroviral therapy (ART) had failed. Only one participant in the drug-naive group had a drug-resistance mutation (M46L), compared with 31.73% of those in whom ART had failed. Further analysis showed that 19.56% of strains contained mutations conferring resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) alone, 0.74% were resistant to nucleoside reverse transcriptase inhibitors (NRTIs) alone, and 11.44% were dual-resistant to both NRTIs and NNRTIs. The most common mutation in the ART-failure group was M184V (35.88%), K103N (45.01%), Y181C (17.33%), and G190S/A (15.88%). The percentages of HIV-1 strains resistant to lamivudine, emtricitabine, efavirenz, etravirine, and nevirapine were 10.70%, 10.70%, 28.04%, 7.75%, and 26.20%, respectively. To explore site variants possibly related to drug resistance, variations in the ancestor/consensus CRF07_BC sequences from the therapy-naive and ART-failure groups were compared, and seven mutations at six positions were identified as being significantly differently distributed between the two groups (p<0.05). Detailed sequence data will provide information on CRF07_BC genetic characterizations, and improve our understanding of antiretroviral susceptibility and the evolution of drug-resistance mutations. This will be valuable in developing and implementing local public-health approaches for HIV drug-resistance prevention and treatment.

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Drug resistance-related mutations T369V/I in the connection subdomain of HIV-1 reverse transcriptase severely impair viral fitness

Wang

Zhang

et al. 2017

Virus Research

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Screening for and Verification of Novel Mutations Associated with Drug Resistance in the HIV Type 1subtype B′ in China

Cited by 3 publications

References 34 publications

In VitroSelection of HIV-1 CRF08_BC Variants Resistant to Reverse Transcriptase Inhibitors

In VitroSelection of HIV-1 CRF08_BC Variants Resistant to Reverse Transcriptase Inhibitors

Prevalence and patterns of drug-resistance mutations among HIV-1 patients infected with CRF07_BC strains in Sichuan province, China

Drug resistance-related mutations T369V/I in the connection subdomain of HIV-1 reverse transcriptase severely impair viral fitness

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