Molecular Epidemiology of Human Immunodeficiency Virus Type 1 in Guangdong Province of Southern China

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Abstract

Background

Although the outbreak of human immunodeficiency virus type 1 (HIV-1) in Guangdong has been documented for more than a decade, the molecular characteristics of such a regional HIV-1 epidemic remained unknown.

Methodology/Principal Findings

By sequencing of HIV-1 pol/env genes and phylogenetic analysis, we performed a molecular epidemiologic study in a representative subset (n = 200) of the 508 HIV-1-seropositive individuals followed up at the center for HIV/AIDS care and treatment of Guangzhou Hospital of Infectious Diseases. Of 157 samples (54.1% heterosexual acquired adults, 20.4% needle-sharing drug users, 5.7% receivers of blood transfusion, 1.3% men who have sex with men, and 18.5% remained unknown) with successful sequencing for both pol and env genes, 105 (66.9%) HIV-1 subtype CRF01_AE and 24 (15.3%) CRF07_BC, 9 (5.7%) B’, 5 (3.2%) CRF08_BC, 5 (3.2%) B, 1 (0.6%) C, 3 (1.9%) CRF02_AG, and 5 (3.2%) inter-region recombinants were identified within pol/env sequences. Thirteen (8.3%) samples (3 naïves, 6 and 5 received with antiretroviral treatment [ART] 1–21 weeks and ≥24 weeks respectively) showed mutations conferring resistance to nucleoside/nonnucleoside reverse transcriptase inhibitors or protease inhibitors. Among 63 ART-naïve patients, 3 (4.8%) showed single or multiple drug resistant mutations. Phylogenetic analysis showed 8 small clusters (2–3 sequences/cluster) with only 17 (10.8%) sequences involved.

Conclusion/Significance

This study confirms that sexual transmission with dominant CRF01_AE strain is a major risk for current HIV-1 outbreak in the Guangdong’s general population. The transmission with drug-resistant variants is starting to emerge in this region.

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Most cited references 27

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Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination.

K Lole, R Bollinger, R S Paranjape … (1999)

The development of an effective human immunodeficiency virus type 1 (HIV-1) vaccine is likely to depend on knowledge of circulating variants of genes other than the commonly sequenced gag and env genes. In addition, full-genome data are particularly limited for HIV-1 subtype C, currently the most commonly transmitted subtype in India and worldwide. Likewise, little is known about sequence variation of HIV-1 in India, the country facing the largest burden of HIV worldwide. Therefore, the objective of this study was to clone and characterize the complete genome of HIV-1 from seroconverters infected with subtype C variants in India. Cocultured HIV-1 isolates were obtained from six seroincident individuals from Pune, India, and virtually full-length HIV-1 genomes were amplified, cloned, and sequenced from each. Sequence analysis revealed that five of the six genomes were of subtype C, while one was a mosaic of subtypes A and C, with multiple breakpoints in env, nef, and the 3' long terminal repeat as determined by both maximal chi2 analysis and phylogenetic bootstrapping. Sequences were compared for preservation of known cytotoxic T lymphocyte (CTL) epitopes. Compared with those of the HIV-1LAI sequence, 38% of well-defined CTL epitopes were identical. The proportion of nonconservative substitutions for Env, at 61%, was higher (P < 0.001) than those for Gag (24%), Pol (18%), and Nef (32%). Therefore, characterized CTL epitopes demonstrated substantial differences from subtype B laboratory strains, which were most pronounced in Env. Because these clones were obtained from Indian seroconverters, they are likely to facilitate vaccine-related efforts in India by providing potential antigens for vaccine candidates as well as for assays of vaccine responsiveness.

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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.

Fujie Zhang, Zhihui Dou, Ye Ma … (2011)

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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Genetic analysis reveals the complex structure of HIV-1 transmission within defined risk groups.

Oliver G. Pybus, Stephane Hue, Deenan Pillay … (2005)

We explored the epidemic history of HIV-1 subtype B in the United Kingdom by using statistical methods that infer the population history of pathogens from sampled gene sequence data. Phylogenetic analysis of HIV-1 pol gene sequences from Britain showed at least six large transmission chains, indicating a genetically variable, but epidemiologically homogeneous, epidemic among men having sex with men. Through coalescent-based analysis, we showed that these chains arose through separate introductions of subtype B strains into the United Kingdom in the early to mid-1980s. After an initial period of exponential growth, the rate of spread generally slowed in the early 1990s, which is more likely to correlate with behavior change than with reduced infectiousness resulting from highly active antiretroviral therapy. Our results provide insights into the complexity of HIV-1 epidemics that must be considered when developing HIV monitoring and prevention initiatives.

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Author and article information

Contributors

Chiyu Zhang: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Electronic): 1932-6203

Publication date Collection: 2012

Publication date (Electronic): 7 November 2012

Volume: 7

Issue: 11

Electronic Location Identifier: e48747

Affiliations

[1 ]Sino-French Collaborative Laboratory, Tropical Medicine Institute, Guangzhou University of Chinese Medicine, Guangzhou, China

[2 ]Laboratoire d’Oncologie et Virologie Moléculaire, Université Paris Descartes, Paris, France

[3 ]Guangzhou Hospital of Infectious Diseases, Guangzhou, China

[4 ]UMI 233, Institut de Recherche pour le Développement and Université de Monpellier 1, Monpellier, France

Institut Pasteur of Shanghai, Chinese Academy of Sciences, China

Author notes

* E-mail: louis.luwei@ 123456ird.fr

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

Conceived and designed the experiments: SC WC JH NV CL WG HH XC LF MP ED JMA WL. Performed the experiments: SC WC JH NV CL WG. Analyzed the data: SC NV WL. Contributed reagents/materials/analysis tools: SC NV WL. Wrote the paper: SC NV WL.

Article

Publisher ID: PONE-D-12-05555

DOI: 10.1371/journal.pone.0048747

PMC ID: 3492446

PubMed ID: 23144953

SO-VID: b5f4410b-8060-4340-a0b2-1cff2969c848

License:

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

Date received : 23 February 2012

Date accepted : 1 October 2012

Page count

Pages: 8

Funding

This work was supported by the Institut de Recherche pour le Développement (IRD) and the Institut de Recherche sur les Vaccins et l’Immunothérapie des Cancers et du Sida (IRVICS). S.C. was supported by a fellowship from Université Paris Descartes. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Molecular Epidemiology of Human Immunodeficiency Virus Type 1 in Guangdong Province of Southern China

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Abstract

Background

Methodology/Principal Findings

Conclusion/Significance

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PLOS Climate

Most cited references 27

Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination.

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

Genetic analysis reveals the complex structure of HIV-1 transmission within defined risk groups.

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