Molecular Epidemiology of HIV in Asia and the Pacific

Tovanabutra, Sodsai; Birx, Deborah L.; McCutchan, Francine E.

doi:10.1007/978-0-306-48536-7_16

Cited by 7 publications

(7 citation statements)

References 109 publications

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“…The CRF01_AE and CRF02_AG strains likewise faithfully represented their respective CRF and mirrored the diversity recognized for these CRF, currently low for CRF01_AE and higher for CRF02_AG (28,65). The envelope sequences verify the faithful propagation of the viruses, reestablish the genetic relationships observed from the complete genome sequences, and provide an envelope sequence proximal to the virus stock that would undergo neutralization analysis.…”

Section: Collection Of Isolatesmentioning

confidence: 58%

“…However, this appears to be reflective of the current molecular epidemiology of this CRF in southeast Asia where intrapatient diversity is still lower than many countries and regions where clades and CRFs are already established (65). In addition, the CRF01_AE viruses were found to contain a lower average number of glycosylation sites with respect to other clades/CRFs within the panel.…”

Section: Discussionmentioning

confidence: 84%

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Biologic and Genetic Characterization of a Panel of 60 Human Immunodeficiency Virus Type 1 Isolates, Representing Clades A, B, C, D, CRF01_AE, and CRF02_AG, for the Development and Assessment of Candidate Vaccines

Brown

Darden

Tovanabutra

et al. 2005

J Virol

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A critical priority for human immunodeficiency virus type 1 (HIV-1) vaccine development is standardization of reagents and assays for evaluation of immune responses elicited by candidate vaccines. To provide a panel of viral reagents from multiple vaccine trial sites, 60 international HIV-1 isolates were expanded in peripheral blood mononuclear cells and characterized both genetically and biologically. Ten isolates each from clades A, B, C, and D and 10 isolates each from CRF01_AE and CRF02_AG were prepared from individuals whose HIV-1 infection was evaluated by complete genome sequencing. The main criterion for selection was that the candidate isolate was pure clade or pure circulating recombinant. After expansion in culture, the complete envelope (gp160) of each isolate was verified by sequencing. The 50% tissue culture infectious dose and p24 antigen concentration for each viral stock were determined; no correlation between these two biologic parameters was found. Syncytium formation in MT-2 cells and CCR5 or CXCR4 coreceptor usage were determined for all isolates. Isolates were also screened for neutralization by soluble CD4, a cocktail of monoclonal antibodies, and a pool of HIV-1-positive patient sera. The panel consists of 49 nonsyncytium-inducing isolates that use CCR5 as a major coreceptor and 11 syncytium-inducing isolates that use only CXCR4 or both coreceptors. Neutralization profiles suggest that the panel contains both neutralization-sensitive and -resistant isolates. This collection of HIV-1 isolates represents the six major globally prevalent strains, is exceptionally large and well characterized, and provides an important resource for standardization of immunogenicity assessment in HIV-1 vaccine trials.

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Section: Collection Of Isolatesmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 84%

Biologic and Genetic Characterization of a Panel of 60 Human Immunodeficiency Virus Type 1 Isolates, Representing Clades A, B, C, D, CRF01_AE, and CRF02_AG, for the Development and Assessment of Candidate Vaccines

Brown

Darden

Tovanabutra

et al. 2005

J Virol

Self Cite

123

105

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“…Due to the early and continuous participation in the planning and execution of HIV-1 vaccine trials, the Thai epidemic is one of the best studied (5). The early 1990s saw a great expansion of the HIV-1 epidemic, with a nationwide seroprevalence among young military conscripts of 3.7%, reaching 12% among those from northern Thailand (6,7).…”

mentioning

confidence: 99%

Molecular Evolution of the HIV-1 Thai Epidemic between the Time of RV144 Immunogen Selection to the Execution of the Vaccine Efficacy Trial

Kijak

Tovanabutra

Rerks-Ngarm

et al. 2013

J Virol

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The RV144 HIV-1 vaccine trial (Thailand, 2003 to 2009), using immunogens genetically matched to the regional epidemic, demonstrated the first evidence of efficacy for an HIV-1 vaccine. Here we studied the molecular evolution of the HIV-1 epidemic from the time of immunogen selection to the execution of the efficacy trial. We studied HIV-1 genetic diversity among 390 volunteers who were deferred from enrollment in RV144 due to preexisting HIV-1 infection using a multiregion hybridization assay, full-genome sequencing, and phylogenetic analyses. The subtype distribution was 91.7% CRF01_AE, 3.5% subtype B, 4.3% B/CRF01_AE recombinants, and 0.5% dual infections. CRF01_AE strains were 31% more diverse than the ones from the 1990s Thai epidemic. Sixty-nine percent of subtype B strains clustered with the cosmopolitan Western B strains. Ninety-three percent of B/CRF01_AE recombinants were unique; recombination breakpoint analysis showed that these strains were highly embedded within the larger network that integrates recombinants from East/Southeast Asia. Compared to Thai sequences from the early 1990s, the distance to the RV144 immunogens increased 52% to 68% for CRF01_AE Env immunogens and 12% to 29% for subtype B immunogens. Forty-three percent to 48% of CRF01_AE sequences differed from the sequence of the vaccine insert in Env variable region 2 positions 169 and 181, which were implicated in vaccine sieve effects in RV144. In conclusion, compared to the molecular picture at the early stages of vaccine development, our results show an overall increase in the genetic complexity of viruses in the Thai epidemic and in the distance to vaccine immunogens, which should be considered at the time of the analysis of the trial results.

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“…In China, India, and Southeast Asia, the main circulating strains are subtypes B, C, and CRF01_AE, respectively, and in each of these areas, the different strains co-circulate in high-risk cohorts, generating multiple inter-subtype recombinants [22]. Most of these recombinants arose among IDUs in the "golden triangle," an opium cultivation hub positioned between Myanmar, Thailand, and Laos and were later introduced into local networks through different drug-trafficking routes.…”

Section: Asia and The Pacificmentioning

confidence: 99%

HIV diversity, molecular epidemiology, and the role of recombination

Kijak

McCutchan²

2005

Curr Infect Dis Rep

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The magnitude of the HIV pandemic and its extensive genetic variation may earn it a unique place among infectious agents. A high mutation rate and a rampant recombination are driving HIV's evolution. Nine subtypes and a variety of recombinant forms of HIV now exist. The source of recombinant forms is the multiple infection of target cells, which becomes highly significant when individuals become infected with two or more divergent strains. In the current paper, we re-examine the role of dual infection and recombination in the generation of HIV-1 diversity, both in individuals and on a global scale. The current molecular epidemiology of HIV-1 is reviewed, emphasizing the latest reports from regional epidemics.

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Molecular Epidemiology of HIV in Asia and the Pacific

Cited by 7 publications

References 109 publications

Biologic and Genetic Characterization of a Panel of 60 Human Immunodeficiency Virus Type 1 Isolates, Representing Clades A, B, C, D, CRF01_AE, and CRF02_AG, for the Development and Assessment of Candidate Vaccines

Biologic and Genetic Characterization of a Panel of 60 Human Immunodeficiency Virus Type 1 Isolates, Representing Clades A, B, C, D, CRF01_AE, and CRF02_AG, for the Development and Assessment of Candidate Vaccines

Molecular Evolution of the HIV-1 Thai Epidemic between the Time of RV144 Immunogen Selection to the Execution of the Vaccine Efficacy Trial

HIV diversity, molecular epidemiology, and the role of recombination

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