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Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China.

Li H, Zhong M, Guo W, Zhuang D, Li L, Liu Y, Bao Z, Liu S, Wang X, Li T, Yang S, Li J - PLoS ONE (2013)

Bottom Line: Assessing the prevalence of HIV-1 drug-resistance and the mutation patterns associated with resistance in the geographical regions implementing free antiretroviral therapy (ART) in China is necessary for preventing the spread of resistant strains and designing the regimens for the subsequent therapies with limited resources.The high prevalence of HIV drug-resistance observed among the ART-failure individuals from 2010 to 2011 in Yunnan province should be of increasing concern in regions where the implementation of ART is widespread.Education about the risk factors associated with HIV drug resistance is important for preventing and controlling the spread of HIV drug-resistant strains.

View Article: PubMed Central - PubMed

Affiliation: Department of AIDS Research, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.

ABSTRACT

Background: Assessing the prevalence of HIV-1 drug-resistance and the mutation patterns associated with resistance in the geographical regions implementing free antiretroviral therapy (ART) in China is necessary for preventing the spread of resistant strains and designing the regimens for the subsequent therapies with limited resources.

Methods: Plasma samples in different cities/prefectures were collected at Yunnan Provincial Hospital of Infectious Disease from January 2010 to December 2011. Genotyping of drug-resistant individuals was conducted using an in-house assay on plasma samples. Viral load, CD4 T cell counts and demographic data were obtained from medical records and an administered questionnaire.

Results: A total of 609 pol sequences (515 ART-failure and 94 therapy-naïve individuals) derived from 664 samples were obtained. The prevalence of drug-resistance was 45.1% in the ART-failure individuals. Of these, 26.8% harbored HIV strains dually resistant to nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors, and 14.8% harbored HIV strains resistant to only one drug category. Mutations such as M184V/I, K103N, V106A, Y181C and G190A were common among the ART-failure individuals, and the frequencies of M184V/I, K103N and V106A were 28.2%, 19.2%, and 22.1%, respectively. The percentages of individuals exhibiting intermediate or high-level resistance to 3TC, FTC, EFV and NVP drugs were 28.4%, 28.2%, 37.3%, and 37.5%, respectively. Factors such as ethnicity, transmission route, CD4 counts, viral load and the duration of ART were significantly correlated with development of drug resistance in the ART-failure individuals.

Conclusions: The high prevalence of HIV drug-resistance observed among the ART-failure individuals from 2010 to 2011 in Yunnan province should be of increasing concern in regions where the implementation of ART is widespread. Education about the risk factors associated with HIV drug resistance is important for preventing and controlling the spread of HIV drug-resistant strains.

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Antiretroviral drug resistance levels among the ART-failure individuals in the Yunnan province in 2010–2011.Note: DRV/r, darunavir with ritonavir; LPV/r, lopinavir with ritonavir; TPV/r, tipranavir with ritonavir; ABC, abacavir; FTC, emtricitabine; ETR, etravirine; DLV, delavirdin.
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pone-0072630-g003: Antiretroviral drug resistance levels among the ART-failure individuals in the Yunnan province in 2010–2011.Note: DRV/r, darunavir with ritonavir; LPV/r, lopinavir with ritonavir; TPV/r, tipranavir with ritonavir; ABC, abacavir; FTC, emtricitabine; ETR, etravirine; DLV, delavirdin.

Mentions: Next, we evaluated the presence of mutations in the HIV pol gene by comparing the sequences against the HIVDR Database from Stanford University to find the known mutations related with drug resistance. The prevalence of drug resistance was 2.1% (2/94) in the control therapy-naïve individuals. One individual that was infected through homosexual contact, exhibited a high level of resistance to nelfinavir with ritonavir (NFV/r) with a D30N mutation and conferred intermediate resistance to all nucleoside reverse transcriptase inhibitors (NRTIs) with T69ins. The other individual infected through heterosexual contact, had mutations of L90M and A71V and exhibited low-level resistance to atazanavir with ritonavir (ATV/r) and fosamprenavir with ritonavir (FPV/r), intermediate resistance to indinavir with ritonavir (IDV/r) and saquinavir with ritonavir (SQV/r), and high resistance to NFV/r. The HIV resistant strains were likely introduced through their sexual partners as neither individual had a previous history of drug use. The frequencies of some mutations, including A71TV, T69S, and V179D were relatively high between the therapy-naive and the ART-failure individuals but the impact on susceptibility to antiviral drugs was low; therefore, these mutations were not described in detail in this study. In contrast to the low prevalence of drug resistance in the therapy-naïve individuals, 45.1% (232/515) of the ART-failure individuals exhibited at least one drug-resistant mutation. Of the 232 individuals (Table 2), six, six and four cases were resistant to all, protease inhibitors (PIs), and NRTIs, respectively. One of the 515 ART-failure cases exhibited dual resistance to PIs and NNRTIs. The majority of individuals were resistant to NNRTIs, 14.8% to NNRTIs alone and 26.8% were dual resistant to NRTIs and NNRTIs. The percentages of resistance to 3TC, FTC, EFV, ETR, and NVP drugs were 28.4%, 28.2%, 39.4%, 25.6% and 39.6% resistance, respectively (Figure 3). Resistance to the other five drugs (ABC, AZT, d4T, ddI, and DLV) was more than 10% each.


Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China.

Li H, Zhong M, Guo W, Zhuang D, Li L, Liu Y, Bao Z, Liu S, Wang X, Li T, Yang S, Li J - PLoS ONE (2013)

Antiretroviral drug resistance levels among the ART-failure individuals in the Yunnan province in 2010–2011.Note: DRV/r, darunavir with ritonavir; LPV/r, lopinavir with ritonavir; TPV/r, tipranavir with ritonavir; ABC, abacavir; FTC, emtricitabine; ETR, etravirine; DLV, delavirdin.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3757030&req=5

pone-0072630-g003: Antiretroviral drug resistance levels among the ART-failure individuals in the Yunnan province in 2010–2011.Note: DRV/r, darunavir with ritonavir; LPV/r, lopinavir with ritonavir; TPV/r, tipranavir with ritonavir; ABC, abacavir; FTC, emtricitabine; ETR, etravirine; DLV, delavirdin.
Mentions: Next, we evaluated the presence of mutations in the HIV pol gene by comparing the sequences against the HIVDR Database from Stanford University to find the known mutations related with drug resistance. The prevalence of drug resistance was 2.1% (2/94) in the control therapy-naïve individuals. One individual that was infected through homosexual contact, exhibited a high level of resistance to nelfinavir with ritonavir (NFV/r) with a D30N mutation and conferred intermediate resistance to all nucleoside reverse transcriptase inhibitors (NRTIs) with T69ins. The other individual infected through heterosexual contact, had mutations of L90M and A71V and exhibited low-level resistance to atazanavir with ritonavir (ATV/r) and fosamprenavir with ritonavir (FPV/r), intermediate resistance to indinavir with ritonavir (IDV/r) and saquinavir with ritonavir (SQV/r), and high resistance to NFV/r. The HIV resistant strains were likely introduced through their sexual partners as neither individual had a previous history of drug use. The frequencies of some mutations, including A71TV, T69S, and V179D were relatively high between the therapy-naive and the ART-failure individuals but the impact on susceptibility to antiviral drugs was low; therefore, these mutations were not described in detail in this study. In contrast to the low prevalence of drug resistance in the therapy-naïve individuals, 45.1% (232/515) of the ART-failure individuals exhibited at least one drug-resistant mutation. Of the 232 individuals (Table 2), six, six and four cases were resistant to all, protease inhibitors (PIs), and NRTIs, respectively. One of the 515 ART-failure cases exhibited dual resistance to PIs and NNRTIs. The majority of individuals were resistant to NNRTIs, 14.8% to NNRTIs alone and 26.8% were dual resistant to NRTIs and NNRTIs. The percentages of resistance to 3TC, FTC, EFV, ETR, and NVP drugs were 28.4%, 28.2%, 39.4%, 25.6% and 39.6% resistance, respectively (Figure 3). Resistance to the other five drugs (ABC, AZT, d4T, ddI, and DLV) was more than 10% each.

Bottom Line: Assessing the prevalence of HIV-1 drug-resistance and the mutation patterns associated with resistance in the geographical regions implementing free antiretroviral therapy (ART) in China is necessary for preventing the spread of resistant strains and designing the regimens for the subsequent therapies with limited resources.The high prevalence of HIV drug-resistance observed among the ART-failure individuals from 2010 to 2011 in Yunnan province should be of increasing concern in regions where the implementation of ART is widespread.Education about the risk factors associated with HIV drug resistance is important for preventing and controlling the spread of HIV drug-resistant strains.

View Article: PubMed Central - PubMed

Affiliation: Department of AIDS Research, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.

ABSTRACT

Background: Assessing the prevalence of HIV-1 drug-resistance and the mutation patterns associated with resistance in the geographical regions implementing free antiretroviral therapy (ART) in China is necessary for preventing the spread of resistant strains and designing the regimens for the subsequent therapies with limited resources.

Methods: Plasma samples in different cities/prefectures were collected at Yunnan Provincial Hospital of Infectious Disease from January 2010 to December 2011. Genotyping of drug-resistant individuals was conducted using an in-house assay on plasma samples. Viral load, CD4 T cell counts and demographic data were obtained from medical records and an administered questionnaire.

Results: A total of 609 pol sequences (515 ART-failure and 94 therapy-naïve individuals) derived from 664 samples were obtained. The prevalence of drug-resistance was 45.1% in the ART-failure individuals. Of these, 26.8% harbored HIV strains dually resistant to nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors, and 14.8% harbored HIV strains resistant to only one drug category. Mutations such as M184V/I, K103N, V106A, Y181C and G190A were common among the ART-failure individuals, and the frequencies of M184V/I, K103N and V106A were 28.2%, 19.2%, and 22.1%, respectively. The percentages of individuals exhibiting intermediate or high-level resistance to 3TC, FTC, EFV and NVP drugs were 28.4%, 28.2%, 37.3%, and 37.5%, respectively. Factors such as ethnicity, transmission route, CD4 counts, viral load and the duration of ART were significantly correlated with development of drug resistance in the ART-failure individuals.

Conclusions: The high prevalence of HIV drug-resistance observed among the ART-failure individuals from 2010 to 2011 in Yunnan province should be of increasing concern in regions where the implementation of ART is widespread. Education about the risk factors associated with HIV drug resistance is important for preventing and controlling the spread of HIV drug-resistant strains.

Show MeSH
Related in: MedlinePlus