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      Population-based human immunodeficiency virus 1 drug resistance profiles among individuals who experienced virological failure to first-line antiretroviral therapy in Henan, China during 2010–2011

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          Abstract

          Background

          In Henan, China, first-line antiretroviral treatment (ART) was implemented early in a large number of treatment-experienced patients who were more likely to have a drug resistance. Therefore, we investigated the human immunodeficiency virus (HIV)-1 drug resistance profiles among patients in Henan who experienced virological failure to ART.

          Method

          A cross-sectional survey was administered in 10 major epidemic cities from May 2010 to October 2011. Adult patients who experienced virological failure (virus load ≥1,000 copies/mL) with >1 year of first-line antiretroviral treatment consented to provide blood for genotype resistance testing. The clinical and demographic data were obtained from the patients’ medical records. Logistic regression analysis was performed to determine the factors associated with ≥1 significant drug resistance mutation.

          Results

          We included 3,235 patients with integral information and valid genotypic resistance data. The city, age, CD4 counts, virus load, treatment duration, and World Health Organization stage were associated with drug resistance, and 64.76% of patients acquired drug resistance. The nucleoside reverse transcriptase inhibitor (NRTI), non-(N)NRTI, and protease inhibitor resistance mutations were found in 50.26, 63.12, and 1.30% of subjects, respectively. Thymidine analogue mutations, NNRTI and even multidrug resistance complex were quite common in this patient cohort.

          Conclusion

          Multiple and complex patterns of HIV-1 drug resistance mutations were identified among individuals who experienced virological failure to first-line ART in Henan, China during 2010–2011. Therefore, timely virological monitoring, therapy adjustments, and more varieties of drugs and individualized treatment should be immediately considered in this patient population.

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          Most cited references26

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          Effect of earlier initiation of antiretroviral treatment and increased treatment coverage on HIV-related mortality in China: a national observational cohort study.

          Overall HIV mortality rates in China have not been reported. In this analysis we assess overall mortality in treatment-eligible adults with HIV and attempt to identify risk factors for HIV-related mortality. We used data from the national HIV epidemiology and treatment databases to identify individuals aged 15 years or older with HIV who were eligible for highly active antiretroviral therapy between 1985 and 2009. Mortality rates were calculated in terms of person-years, with risk factors determined by Cox proportional hazard regression. Treatment coverage was calculated as the proportion of time that patients who were eligible for treatment received treatment, with risk factors for not receiving treatment identified by use of logistic regression. Of 323,252 people reported as having HIV in China by the end of 2009, 145,484 (45%) were identified as treatment-eligible and included in this analysis. Median CD4 count was 201 cells per μL (IQR 71-315) at HIV diagnosis and 194 cells per μL (73-293) when first declared eligible for treatment. Overall mortality decreased from 39·3 per 100 person-years in 2002 to 14·2 per 100 person-years in 2009, with treatment coverage concomitantly increasing from almost zero to 63·4%. By 2009, mortality was higher and treatment coverage lower in injecting drug users (15·9 deaths per 100 person-years; 42·7% coverage) and those infected sexually (17·5 deaths per 100 person-years; 61·7% coverage), compared with those infected through plasma donation or blood transfusion (6·7 deaths per 100 person-years; 80·2% coverage). The two strongest risk factors for HIV-related mortality were not receiving highly active antiretroviral therapy (adjusted hazard ratio 4·35, 95% CI 4·10-4·62) and having a CD4 count of less than 50 cells per μL when first declared eligible for treatment (7·92, 7·33-8.57). An urgent need exists for earlier HIV diagnosis and better access to treatment for injecting drug users and patients infected with HIV sexually, especially before they become severely immunosuppressed. The National Centre for AIDS/STD Control and Prevention of the Chinese Centre for Disease Control and Prevention. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            HIV prevalence in China: integration of surveillance data and a systematic review.

            Asian HIV epidemics are concentrated among particular behavioural groups, but large variations exist in epidemic types, timing, and geographical spread between countries and within countries, especially in China. We aimed to understand the complexity of HIV epidemics in China by systematically analysing prevalence trends by data source, region, population group, and time period. We collected HIV prevalence data from official national sentinel surveillance sites at the provincial level from Jan 1, 1995, to Dec 31, 2010. We also searched PubMed, VIP Chinese Journal Database (VIP), China National Knowledge Infrastructure, and Wanfang Data from Jan 1, 1990, to Dec 31, 2012, for independent studies of HIV prevalence. We integrated both sets of data, and used an intraclass correlation coefficient test to assess the similarity of geographical pattern of HIV disease burden across 31 Chinese provinces in 2010. We investigated prevalence trends (and 95% CIs) to infer corresponding incidence by region, population group, and year. Of 6850 articles identified by the search strategy, 821 studies (384,583 drug users, 52,356 injecting drug users, 186,288 female sex workers, and 87,834 men who have sex with men) met the inclusion criteria. Official surveillance data and findings from independent studies showed a very similar geographical distribution and magnitude of HIV epidemics across China. We noted that HIV epidemics among injecting drug users are decreasing in all regions outside southwest China and have stabilised at a high level in northwest China. Compared with injecting drug users, HIV prevalence in female sex workers is much lower and has stabilised at low levels in all regions except in the southwest. In 2010, national HIV prevalence was 9·08% (95% CI 8·04-10·52) in injecting drug users and 0·36% (0·12-0·71) in female sex workers, whereas incidence in both populations stabilised at rates of 0·57 (0·43-0·72) and 0·02 (0·01-0·04) per 100 person-years, respectively. By comparison, HIV prevalence in men who have sex with men increased from 1·77% (1·26-2·57) in 2000, to 5·98% (4·43-8·18) in 2010, with a national incidence of 0·98 (0·70-1·25) per 100 person-years in 2010. We recorded strong associations between HIV prevalence among at-risk populations in each province, supporting the existence of overlap in risk behaviours and mixing among these populations. HIV epidemics in China remain concentrated in injecting drug users, female sex workers, and men who have sex with men. HIV prevalence is especially high in southwest China. Sex between men has clearly become the main route of HIV transmission. Copyright © 2013 Elsevier Ltd. All rights reserved.
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              Virological follow-up of adult patients in antiretroviral treatment programmes in sub-Saharan Africa: a systematic review.

              Following large-scale roll-out of antiretroviral therapy in sub-Saharan Africa, the non-clinical efficacy of antiretroviral therapy has received little attention. We aimed to systematically review virological efficacy and drug-resistance outcomes of programmes of antiretroviral therapy in sub-Saharan Africa. 89 studies with heterogeneous design, definitions, and methods were identified. Overall, in on-treatment analysis, 10 351 (78%) of 13 288 patients showed virological suppression after 6 months of antiretroviral therapy, 7413 (76%) of 9794 after 12 months, and 3840 (67%) of 5690 after 24 months. Long-term virological data are scarce. Genotyping results were available for patients with virological failure (HIV-1 RNA greater than 1000 copies per mL). Most patients (839 of 849; 99%) were infected with a non-B HIV-1 subtype. However, drug-resistance patterns were largely similar to those in subtype B. Resistance profiles were associated with the antiretroviral drugs commonly used: the lamivudine-associated M184V mutation was most common, followed by K103N which is associated with non-nucleoside reverse transcriptase inhibitors. Thymidine-analogue mutations and the K65R mutation were less common. First-line antiretroviral therapy regimens used in sub-Saharan Africa are effective. Profiles of drug resistance suggest that a second-line treatment regimen based on protease inhibitors, with a backbone of nucleoside reverse transcriptase inhibitors, is a reasonable option for patients with HIV in sub-Saharan Africa who experience first-line treatment failure. 2010 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                dhelix@163.com
                yasongwu5@163.com
                wenjie0924@126.com
                boboo2009@126.com
                sungq2002@163.com
                chunhua5167@sina.com
                tiansa@hncdc.com.cn
                sundy@hncdc.com.cn
                zhuq@hncdc.com.cn
                wangzhe@hncdc.com.cn
                Journal
                AIDS Res Ther
                AIDS Res Ther
                AIDS Research and Therapy
                BioMed Central (London )
                1742-6405
                27 June 2015
                27 June 2015
                2015
                : 12
                : 22
                Affiliations
                [ ]Henan Center for Disease Control and Prevention, Zhengzhou, Henan China
                [ ]Chinese Center for Disease Control and Prevention, Beijing, China
                Article
                62
                10.1186/s12981-015-0062-y
                4483220
                bb4226a9-8327-493f-8fe3-c189d627d30a
                © Liu et al. 2015

                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/h) applies to the data made available in this article, unless otherwise stated.

                History
                : 27 March 2015
                : 12 June 2015
                Categories
                Research
                Custom metadata
                © The Author(s) 2015

                Infectious disease & Microbiology
                hiv,drug resistance,first-line antiretroviral therapy,virological failure

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