Dataset Information

The prevalence of HIV-1 drug resistance among antiretroviral treatment naive individuals in mainland China: a meta-analysis.

ABSTRACT: BACKGROUND: Surveillance of drug resistance in antiretroviral treatment-naïve patients in China is needed to ensure optimal treatment outcomes and control of the human immunodeficiency virus (HIV) epidemic. METHODS: A systematic literature search was conducted in English and Chinese through PubMed (English), China National Knowledge Infrastructure (Chinese), Chinese Biomedical Literature Database (Chinese), and Wanfang (Chinese). Random effects models were used to calculate the pooled prevalence of transmitted drug resistance and subgroup analyses examined prevalence estimates across time periods, study locations, and study populations. RESULTS: Analysis of data from 71 studies (47 in Chinese and 24 in English) yielded a pooled prevalence of transmitted HIV drug resistance to any antiretroviral drug class of 3.64% (95% confidence interval [CI]: 3.00%-4.32%). Rates were significantly high at initial stage of free ART program from 2003 to 2005 (5.18%, 95%CI: 3.13%-7.63%), and were much lower among studies conducted in 2006-2008 (3.02%, 95%CI: 2.03%-4.16%). A slight increase was observed again in the most recent study period from 2009 to 2012 (3.68%, 95%CI: 2.78%-4.69%). Subgroup analysis revealed highest prevalence levels of transmitted drug resistance in Beijing city, and Henan and Hubei provinces (above 5%), and although differences in prevalence rates among risk groups were negligible, men who have sex with men were unique in their relatively large portion of protease inhibitor resistance, a second-line drug of limited availability in China. CONCLUSIONS: Overall prevalence of transmitted HIV drug resistance in China is classified as "low" by the World Health Organization. However regional and temporal variability suggest a more complex epidemic for which closer HIV drug resistance surveillance is needed. A nationwide HIV drug resistance surveillance system to monitor both treatment-experienced and treatment-naïve patients will be a cornerstone to ensure the effectiveness of treatment scale-up, particularly as China seeks to expand a national policy of antiretroviral treatment as prevention.

SUBMITTER: Su Y

PROVIDER: S-EPMC4208788 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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The prevalence of HIV-1 drug resistance among antiretroviral treatment naïve individuals in mainland China: a meta-analysis.

Su Yingying Y Zhang Fujie F Liu Huixin H Smith M Kumi MK Zhu Lin L Wu Jing J Wang Ning N

PloS one 20141024 10

<h4>Background</h4>Surveillance of drug resistance in antiretroviral treatment-naïve patients in China is needed to ensure optimal treatment outcomes and control of the human immunodeficiency virus (HIV) epidemic.<h4>Methods</h4>A systematic literature search was conducted in English and Chinese through PubMed (English), China National Knowledge Infrastructure (Chinese), Chinese Biomedical Literature Database (Chinese), and Wanfang (Chinese). Random effects models were used to calculate the pool ...[more]

PMID: 25343483

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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.

Project description:BackgroundIncreasing HIV pre-treatment drug resistance (PDR) levels have been observed in regions with increasing antiretroviral treatment (ART) coverage. However, data is lacking for several low/middle-income countries. We present the first PDR survey in Nicaragua since ART introduction in the country in 2003.MethodsHIV-infected, ART-naïve Nicaraguan individuals were enrolled at Roberto Calderón Hospital, the largest national HIV referral center, from 2011 to 2015. HIV pol sequences were obtained at a WHO-accredited laboratory in Mexico by Sanger and next generation sequencing (NGS). PDR was assessed using the WHO surveillance drug resistance mutation (SDRM) list and the Stanford HIVdb tool.Results283 individuals were enrolled in the study. The overall PDR prevalence based on the list of SDRMs was 13.4%. Using the Stanford HIVdb tool, overall PDR reached 19.4%; with both nucleoside and non-nucleoside reverse transcriptase inhibitor (NRTI and NNRTI) PDR levels independently reaching moderate levels (6.7% and 11.3% respectively). Protease inhibitor PDR was low (2.8%). Using NGS with 2% threshold to detect SDRMs, PDR increased to 25.3%. K103N and M41L were the most frequent SDRMs and were present mostly in proportions >20% in each individual. A significant temporal increase in NNRTI PDR was observed (p = 0.0422), with no apparent trends for other drug classes. Importantly, PDR to zidovudine + lamivudine + efavirenz and tenofovir + emtricitabine + efavirenz, the most widely used first-line regimens in Nicaragua, reached 14.6% and 10.4% respectively in 2015. Of note, a higher proportion of females was observed among individuals with PDR compared to individuals without PDR (OR 14.2; 95% CI: 7.1-28.4; p<0.0001).ConclusionsOverall PDR in the Nicaraguan cohort was high (19.4%), with a clear increasing temporal trend in NNRTI PDR. Current HIVDR to the most frequently used first-line ART regimens in Nicaragua reached levels >10%. These observations are worrisome and need to be evidenced to strengthen the national HIV program. Also, our observations warrant further nationally representative HIVDR surveillance studies and encourage other countries to perform national surveys. Cost-effectiveness studies are suggested to analyze the feasibility of implementation of baseline HIV genotyping as well as to review the choice of first-line ART regimens in Nicaragua.

Project description:BackgroundThere are few data on the prevalence of WHO transmitted drug resistance mutations (TDRs) that could affect treatment responses to first line antiretroviral therapy (ART) in Hunan Province, China.ObjectiveDetermine the prevalence of WHO NRTI/NNRTI/PI TDRs in ART-naïve subjects in Hunan Province by deep sequencing.MethodsART-naïve subjects diagnosed in Hunan between 2010-2011 were evaluated by deep sequencing for low-frequency HIV variants possessing WHO TDRs to 1% levels. Mutations were scored using the HIVdb.stanford.edu algorithm to infer drug susceptibility.ResultsDeep sequencing was performed on samples from 90 ART-naïve subjects; 83.3% were AE subtype. All subjects had advanced disease (average CD4 count 134 cells/mm3). Overall 25.6%(23/90) of subjects had HIV with major WHO NRTI/NNRTI TDRs by deep sequencing at a variant frequency level ≥ 1%; 16.7%(15/90) had NRTI TDR and 12.2%(11/90) had a major NNRTI TDR. The majority of NRTI/NNRTI mutations were identified at variant levels <5%. Mutations were analyzed by HIVdb.stanford.edu and 7.8% of subjects had variants with high-level nevirapine resistance; 4.4% had high-level NRTI resistance. Deep sequencing identified 24(27.6%) subjects with variants possessing either a PI TDR or hivdb.stanford.edu PI mutation (algorithm value ≥ 15). 17(19.5%) had PI TDRs at levels >1%.ConclusionsART-naïve subjects from Hunan Province China infected predominantly with subtype AE frequently possessed HIV variants with WHO NRTI/NNRTI TDRs by deep sequencing that would affect the first line ART used in the region. Specific mutations conferring nevirapine high-level resistance were identified in 7.8% of subjects. The majority of TDRs detected were at variant levels <5% likely due to subjects having advanced chronic disease at the time of testing. PI TDRs were identified frequently, but were found in isolation and at low variant frequency. As PI/r use is infrequent in Hunan, the existence of PI mutations likely represent AE subtype natural polymorphism at low variant level frequency.

Dataset Information

The prevalence of HIV-1 drug resistance among antiretroviral treatment naive individuals in mainland China: a meta-analysis.

Publications

The prevalence of HIV-1 drug resistance among antiretroviral treatment naïve individuals in mainland China: a meta-analysis.

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