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Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance.

ABSTRACT: Genotypic surveys suggest that human immunodeficiency virus type 1 (HIV-1) and HIV-2 evolve different sets of mutations in response to nucleoside reverse-transcriptase inhibitors (NRTIs). We used site-directed mutagenesis, culture-based phenotyping, and cell-free assays to determine the resistance profiles conferred by specific amino acid replacements in HIV-2 reverse transcriptase. Although thymidine analogue mutations had no effect on zidovudine sensitivity, the addition of Q151M together with K65R or M184V was sufficient for high-level resistance to both lamivudine and zidovudine in HIV-2, and the combination of K65R, Q151M, and M184V conferred classwide NRTI resistance. These data suggest that current NRTI-based regimens are suboptimal for treating HIV-2 infection.

SUBMITTER: Smith RA

PROVIDER: S-EPMC3726187 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance.

Smith Robert A RA Anderson Donovan J DJ Pyrak Crystal L CL Preston Bradley D BD Gottlieb Geoffrey S GS

The Journal of infectious diseases 20090501 9

Genotypic surveys suggest that human immunodeficiency virus type 1 (HIV-1) and HIV-2 evolve different sets of mutations in response to nucleoside reverse-transcriptase inhibitors (NRTIs). We used site-directed mutagenesis, culture-based phenotyping, and cell-free assays to determine the resistance profiles conferred by specific amino acid replacements in HIV-2 reverse transcriptase. Although thymidine analogue mutations had no effect on zidovudine sensitivity, the addition of Q151M together with ...[more]

PMID: 19358668

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Project description:The efficacy of antiretroviral drugs is limited by the development of drug resistance. Therefore, it is important to examine HIV drug resistance following the nationwide implementation of drug resistance testing in China since 2009. We conducted drug resistance testing in patients who were already on or new to HIV antiretroviral therapy (ART) in Shandong Province, China, from 2011 to 2013, and grouped them based on the presence or absence of drug resistance to determine the effects of age, gender, ethnicity, marital status, educational level, route of transmission and treatment status on drug resistance. We then examined levels of drug resistance the following year. The drug resistance rates of HIV patients on ART in Shandong from 2011 to 2013 were 3.45% (21/608), 3.38% (31/916), and 4.29% (54/1259), per year, respectively. M184V was the most frequently found point mutation, conferring resistance to the nucleoside reverse transcriptase inhibitor, while Y181C, G190A, K103N and V179D/E/F were the most frequent point mutations conferring resistance to the non-nucleoside reverse transcriptase inhibitor. In addition, the protease inhibitor drug resistance mutations I54V and V82A were identified for the first time in Shandong Province. Primary resistance accounts for 20% of the impact factors for drug resistance. Furthermore, it was found that educational level and treatment regimen were high-risk factors for drug resistance in 2011 (P<0.05), while treatment regimen was a high risk factor for drug resistance in 2012 and 2013 (P<0.05). Among the 106 drug-resistant patients, 77 received immediate adjustment of treatment regimen following testing, and 69 (89.6%) showed a reduction in drug resistance the following year. HIV drug resistance has a low prevalence in Shandong Province. However, patients on second line ART regimens and those with low educational level need continuous monitoring. Active drug resistance testing can effectively prevent the development of drug resistance.

Dataset Information

Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance.

Publications

Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance.

Similar Datasets

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