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      HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China

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          Abstract

          Background

          To understand HIV-1 drug resistance in 11 prefectures of Hebei Province, China, we implemented a cross-sectional HIV-1 molecular epidemiological survey.

          Methods

          Blood samples were collected from 122 newly diagnosed drug-naïve HIV-1-positive individuals and 229 antiretroviral therapy (ART)-failure individuals from 11 prefectures in Hebei Province, China. Patient demographic data were obtained via face-to-face interviews using a standardized questionnaire when blood samples were collected. Genotyping of HIV-1 drug resistance (DR) was implemented using an in-house assay.

          Results

          In this study, the overall prevalence of HIV-1 DR was 35.5%. The prevalence of HIV-1 DR in participants experiencing treatment failure and ART-naïve participants was 51.9 and 5.9%, respectively. Mutations in protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs), and non-NRTI (NNRTIs), as well as dual and multiple mutations were extensively seen in participants experiencing treatment failure. The proportions of NNRTI mutations (χ 2 = 9.689, p = 0.002) and dual mutations in NRTIs and NNRTIs (χ 2 = 39.958, p < 0.001) in participants experiencing treatment failure were significantly higher than those in ART-naïve participants. The distributions of M184V/I and M41L mutations differed significantly among three main HIV-1 genotypes identified. Viral load, symptoms in the past 3 months, CD4 counts, transmission route, and the duration of ART were found to be associated with HIV-1 DR.

          Conclusions

          Our results suggest that new prevention and control strategies should be formulated according to the epidemic characteristics of HIV-1-resistant strains in Hebei Province, where antiretroviral drugs are widely used.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12981-017-0133-3) contains supplementary material, which is available to authorized users.

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          Most cited references27

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          Evolution of China's response to HIV/AIDS

          Zunyou Wu, Sheena Sullivan, Yu. Wang … (2007)
          Summary Four factors have driven China's response to the HIV/AIDS pandemic: (1) existing government structures and networks of relationships; (2) increasing scientific information; (3) external influences that underscored the potential consequences of an HIV/AIDS pandemic and thus accelerated strategic planning; and (4) increasing political commitment at the highest levels. China's response culminated in legislation to control HIV/AIDS—the AIDS Prevention and Control Regulations. Three major initiatives are being scaled up concurrently. First, the government has prioritised interventions to control the epidemic in injection drug users, sex workers, men who have sex with men, and plasma donors. Second, routine HIV testing is being implemented in populations at high risk of infection. Third, the government is providing treatment for infected individuals. These bold programmes have emerged from a process of gradual and prolonged dialogue and collaboration between officials at every level of government, researchers, service providers, policymakers, and politicians, and have led to decisive action.
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            Five-year outcomes of the China National Free Antiretroviral Treatment Program.

            Fujie Zhang, Zhihui Dou, Ye Ma … (2009)
            China's National Free Antiretroviral Treatment Program began in 2002 and, by August 2008, included more than 52 000 patients. To report 5-year outcomes on adult mortality and immunologic treatment failure rates and risk factors. Open cohort analysis of a prospectively collected, observational database. China. All patients in the national treatment database from June 2002 to August 2008. Patients were excluded if they had not started triple therapy or had missing treatment regimen information. Antiretroviral therapy according to Chinese national treatment guidelines. Mortality rate and immunologic treatment failure rate, according to World Health Organization criteria. Of 52 191 patients, 48 785 were included. Median age was 38 years, 58% were men, 53% were infected through plasma or blood, and the median baseline CD4 cell count was 0.118x10(9) cells/L. Mortality was greatest during the first 3 months of treatment (22.6 deaths per 100 person-years) but decreased to a steady rate of 4 to 5 deaths per 100 person-years after 6 months and maintained this rate over the subsequent 4.5 years. The strongest mortality risk factors were a baseline CD4 cell count less than 0.050x10(9) cells/L (adjusted hazard ratio [HR] compared with a count>or=0.200x10(9) cells/L, 3.3 [95% CI, 2.9 to 3.8]) and having 4 to 5 baseline symptom categories (adjusted HR compared with no baseline symptom categories, 3.4 [CI, 2.9 to 4.0]). Treatment failure was determined among 31 070 patients with 1 or more follow-up CD4 cell counts. Overall, treatment failed for 25% of patients (12.0 treatment failures per 100 person-years), with the cumulative treatment failure rate increasing to 50% at 5 years. Immunologic treatment failure does not necessarily correlate well with virologic treatment failure. The National Free Antiretroviral Treatment Program reduced mortality among adult patients in China with AIDS to rates similar to those of other low- or middle-income countries. A cumulative immunologic treatment failure rate of 50% after 5 years, due to the limited availability of second-line regimens, is of great concern.
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              A Comprehensive Mapping of HIV-1 Genotypes in Various Risk Groups and Regions across China Based on a Nationwide Molecular Epidemiologic Survey

              Xiang He, Hui-Hui Xing, Yuhua Ruan … (2012)
              Background China is experiencing a dynamic HIV/AIDS epidemic. While serology based surveillance systems have reported the spread of HIV/AIDS, detailed tracking of its transmission in populations and regions is not possible without mapping it at the molecular level. We therefore conducted a nationwide molecular epidemiology survey across the country. Methods HIV-1 genotypes were determined from 1,408 HIV-positive persons newly diagnosed in 2006. The prevalence of each genotype was estimated by weighting the genotype’s prevalence from each province- and risk-specific subpopulation with the number of reported cases in the corresponding subgroups in that year. Results CRF07_BC (35.5%), CRF01_AE (27.6%), CRF08_BC (20.1%), and subtype B' (9.6%) were the four main HIV-1 strains in China. CRF07_BC and CRF08_BC were the primary drivers of infection among injecting drug users in northeastern and southeastern China, respectively, and subtype B' remained dominant among former plasma donors in central China. In contrast, all four strains occurred in significant proportions among heterosexuals nationwide, pointing to an expansion of the HIV-1 epidemic from high-risk populations into the general population. CRF01_AE also replaced subtype B as the principal driver of infection among men-who-have-sex-with-men. Conclusions Our study provides the first comprehensive baseline data on the diversity and characteristics of HIV/AIDS epidemic in China, reflecting unique region- and risk group-specific transmission dynamics. The results provide information critical for designing effective prevention measures against HIV transmission.
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                Author and article information

                Contributors
                Xinli Lu: lxlii2009@163.com
                Hongru Zhao: lxli0124@163.com
                Yuqi Zhang: yqzhang688@163.com
                Wei Wang: lxlii2015@163.com
                Cuiying Zhao: zhaocuiying906@sina.com
                Yan Li: hbstd666@163.com
                Lin Ma: maixiangxiyu@126.com
                Ze Cui: +86-311-86573441 , hbcdc888@163.com
                Suliang Chen: +86-311-86573441 , hebeicdc2013@sina.com
                Journal
                Journal ID (nlm-ta): AIDS Res Ther
                Journal ID (iso-abbrev): AIDS Res Ther
                Title: AIDS Research and Therapy
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1742-6405
                Publication date (Electronic): 23 January 2017
                Publication date PMC-release: 23 January 2017
                Publication date Collection: 2017
                Volume: 14
                Electronic Location Identifier: 4
                Affiliations
                Hebei Provincial Center for Disease Control and Prevention, 97 Huaian East Road, Yuhua District, Shijiazhuang, 050021 China
                Article
                Publisher ID: 133
                DOI: 10.1186/s12981-017-0133-3
                PMC ID: 5260017
                PubMed ID: 28114955
                SO-VID: 81b3f617-0102-4fa6-ba55-99e245c1d6e2
                Copyright © © The Author(s) 2017
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 8 November 2016
                Date accepted : 12 January 2017
                Funding
                Funded by: Our study was implemented with the support of the Natural Science Fund of Hebei Province
                Award ID: H2016303006
                Award Recipient :
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2017

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: hiv-1,mutation,phylogeny,drug resistance,china
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: hiv-1, mutation, phylogeny, drug resistance, china

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