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      HIV-1 Genetic Diversity and Its Impact on Baseline CD4+T Cells and Viral Loads among Recently Infected Men Who Have Sex with Men in Shanghai, China

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          Abstract

          The HIV-1 epidemic among men who have sex with men (MSM) has been spreading throughout China. Shanghai, a central gathering place for MSM, is facing a continuously increasing incidence of HIV-1 infection. In order to better understand the dynamics of HIV-1 diversity and its influence on patient’s immune status at baseline on diagnosis, 1265 newly HIV-1-infected MSM collected from January 2009 to December 2013 in Shanghai were retrospectively analyzed for genetic subtyping, CD4+T cell counts, and viral loads. HIV-1 phylogenetic analysis revealed a broad viral diversity including CRF01_AE (62.13%), CRF07_BC (24.51%), subtype B (8.06%), CRF55_01B (3.24%), CER67_01B (0.95%), CRF68_01B (0.4%), CRF08_BC (0.08%) and CRF59_01B (0.08%). Twenty-four unique recombination forms (URFs) (1.98%) were identified as well. Bayesian inference analysis indicated that the introduction of CRF01_AE strain (1997) was earlier than CRF07_BC strain (2001) into MSM population in Shanghai based on the time of the most recent common ancestor (tMRCA). Three epidemic clusters and five sub-clusters were found in CRF01_AE. Significantly lower CD4+T cell count was found in individuals infected with CRF01_AE than in those infected with CRF07_BC infection ( P<0.01), whereas viral load was significantly higher those infected with CRF01_AE than with CRF07_BC ( P<0.01). In addition, the patients with >45 years of age were found to have lower CD4+T cell counts and higher viral loads than the patients with <25 years of age ( P<0.05). This study reveals the presence of HIV-1 subtype diversity in Shanghai and its remarkable influence on clinical outcome. A real-time surveillance of HIV-1 viral diversity and phylodynamics of epidemic cluster, patient’s baseline CD4+T cell count and viral load would be of great value to monitoring of disease progression, intervention for transmission, improvement of antiretroviral therapy strategy and design of vaccines.

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          1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults.

          (1992)
          CDC has revised the classification system for HIV infection to emphasize the clinical importance of the CD4+ T-lymphocyte count in the categorization of HIV-related clinical conditions. This classification system replaces the system published by CDC in 1986 (1) and is primarily intended for use in public health practice. Consistent with the 1993 revised classification system, CDC has also expanded the AIDS surveillance case definition to include all HIV-infected persons who have < 200 CD4+ T-lymphocytes/microL, or a CD4+ T-lymphocyte percentage of total lymphocytes of < 14. This expansion includes the addition of three clinical conditions--pulmonary tuberculosis, recurrent pneumonia, and invasive cervical cancer--and retains the 23 clinical conditions in the AIDS surveillance case definition published in 1987 (2); it is to be used by all states for AIDS case reporting effective January 1, 1993.
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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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              Five-year outcomes of the China National Free Antiretroviral Treatment Program.

              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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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                29 June 2015
                2015
                : 10
                : 6
                : e0129559
                Affiliations
                [1 ]Department AIDS and STD, Shanghai Municipal Center for Disease Control and Prevention, Shanghai Municipal Institutes for Preventive Medicine, Shanghai, China
                [2 ]Public Health College, Nantong University, Nantong, Jiangsu Province, China
                [3 ]Department of Pathology, New York University School of Medicine, New York, United States of America
                Fudan University, CHINA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: PZ X. Zhuang QP. Performed the experiments: XL Y. Xue HC YL X. Li JG WZ FS XW. Analyzed the data: XL PZ YW HC LK PN MZ. Contributed reagents/materials/analysis tools: LZ ZN XY X. Zheng. Wrote the paper: PZ PN XL.

                Article
                PONE-D-14-56477
                10.1371/journal.pone.0129559
                4486722
                26121491
                a30bdfcf-9772-464c-b57f-8e00f08621c7
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 30 January 2015
                : 10 May 2015
                Page count
                Figures: 4, Tables: 2, Pages: 15
                Funding
                This study was funded by the National Science and Technology Major Project for Infectious Disease Control and Prevention (2012-ZX10001-002), National Natural Science Foundation of China (81373060), The six major human resources project of Jiangsu province (WSN-015). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                Data of CD4 cell counts and viral loads are available as Supporting Information. Sequence Accession numbers from GenBank are: KR187186-KR188450.

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