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Failure to restore the Vgamma2-Jgamma1.2 repertoire in HIV-infected men receiving highly active antiretroviral therapy (HAART).

ABSTRACT: Gammadelta (gammadelta) T cells expressing the Vgamma2-Jgamma1.2Vdelta2 (Vgamma9-JPVdelta2, alternate nomenclature) T cell receptor (TCR) constitute the major peripheral blood population of gammadelta T cells in adult humans and are specifically depleted during human immunodeficiency virus (HIV) disease. Vgamma2-Jgamma1.2Vdelta2 T cells provide a convenient model for assessing the impact of antiretroviral therapy on cell populations that are not susceptible to direct infection because they do not express CD4 and depletion occurs by indirect mechanisms. We obtained longitudinal PBMC samples from 16 HIV-infected individuals who enrolled in the Multicenter AIDS Cohort Study (MACS) and were starting highly active antiretroviral therapy (HAART). Vgamma2-Jgamma1.2Vdelta2 T cells were depleted in these individuals as a result of HIV infection. Despite evidence for clinical benefits of HAART, the Vgamma2-Jgamma1.2Vdelta2 T cell repertoire did not recover after HAART initiation irrespective of treatment duration. These studies highlight important defects among cell subsets lost due to indirect effects of HIV.

SUBMITTER: Hebbeler AM

PROVIDER: S-EPMC2603626 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Failure to restore the Vgamma2-Jgamma1.2 repertoire in HIV-infected men receiving highly active antiretroviral therapy (HAART).

Hebbeler Andrew M AM Propp Nadia N Cairo Cristiana C Li Haishan H Cummings Jean Saville JS Jacobson Lisa P LP Margolick Joseph B JB Pauza C David CD

Clinical immunology (Orlando, Fla.) 20080707 3

Gammadelta (gammadelta) T cells expressing the Vgamma2-Jgamma1.2Vdelta2 (Vgamma9-JPVdelta2, alternate nomenclature) T cell receptor (TCR) constitute the major peripheral blood population of gammadelta T cells in adult humans and are specifically depleted during human immunodeficiency virus (HIV) disease. Vgamma2-Jgamma1.2Vdelta2 T cells provide a convenient model for assessing the impact of antiretroviral therapy on cell populations that are not susceptible to direct infection because they do no ...[more]

PMID: 18606571

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Project description:BackgroundMinimizing antiretroviral treatment failure is crucial for improving patient health and for maintaining long-term access to care in low-income settings such as eastern Africa. To develop interventions to support adherence, policymakers must understand the extent and scope of treatment failure in their programs. However, estimates of treatment failure in eastern Africa have been variable and inconclusive.ObjectiveThis systematic review and meta-analysis sought to determine the pooled prevalence of immunological failure among adults receiving antiretroviral therapy in eastern Africa.MethodsWe performed a systematic search of the PubMed, Google Scholar, Excerpta Medica Database, and the World Health Organization's Hinari portal (which includes the Scopus, African Index Medicus, and African Journals Online databases) databases. Unpublished studies were also accessed from conference websites and university repositories. We used Stata version 14 for data analysis. The Cochrane Q test and I 2 test statistic were used to test for heterogeneity across the studies. Due to high levels of heterogeneity, a random effects model was used to estimate the pooled prevalence of immunological failure. Begg and Egger tests of the intercept in the random effects model were used to check for publication bias.ResultsAfter removing duplicates, 25 articles remained for assessment and screening. After quality screening, 15 articles were deemed eligible and incorporated into the final analysis. The average pooled estimate of immunological treatment failure prevalence was found to be 21.89% (95% CI, 15.14-28.64). In the subgroup analysis conducted by geographic region, the pooled prevalence of immunological treatment failure in Ethiopia was 15.2% (95% CI, 12.27-18.13) while in Tanzania it was 53.93% (95% CI, 48.14-59.73). Neither the results of Egger test or Begg tests suggested publication bias; however, on visual examination, the funnel plot appeared asymmetric. The large heterogeneity across the studies could be explained by study country.ConclusionImmunological treatment failure among patients receiving antiretroviral therapy in eastern Africa was high, and greater than previously reported. The relatively low rates of treatment failure found in Ethiopia suggest that its health extension program should be studied as a model for improving adherence in the region. (Curr Ther Res Clin Exp. 2021; 82:XXX-XXX) © 2021 Elsevier HS Journals, Inc.

Dataset Information

Failure to restore the Vgamma2-Jgamma1.2 repertoire in HIV-infected men receiving highly active antiretroviral therapy (HAART).

Publications

Failure to restore the Vgamma2-Jgamma1.2 repertoire in HIV-infected men receiving highly active antiretroviral therapy (HAART).

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