Initiation of antiretroviral therapy during primary HIV-1 infection induces rapid stabilization of the T-cell receptor beta chain repertoire and reduces the level of T-cell oligoclonality. NLM AIDSLINE Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.

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Initiation of antiretroviral therapy during primary HIV-1 infection induces rapid stabilization of the T-cell receptor beta chain repertoire and reduces the level of T-cell oligoclonality.

Blood. 2000 Mar 1;95(5):1743-51. Unique Identifier : AIDSLINE MED/20156011
Soudeyns H; Campi G; Rizzardi GP; Lenge C; Demarest JF; Tambussi G; Lazzarin A; Kaufmann D; Casorati G; Corey L; Pantaleo G; Laboratory of AIDS Immunopathogenesis, Division of Infectious; Diseases, Department of Internal Medicine, Centre Hospitalier; Universitaire Vaudois, Lausanne, Switzerland.

Abstract: Major T-cell receptor beta chain variable region (TCRBV) repertoire perturbations are temporally associated with the down-regulation of viremia during primary human immunodeficiency virus (HIV) infection and with oligoclonal expansion and clonal exhaustion of HIV-specific cytotoxic T lymphocytes (CTLs). To determine whether initiation of antiretroviral therapy (ART) or highly active antiretroviral therapy (HAART) during primary infection influences the dynamics of T-cell-mediated immune responses, the TCRBV repertoire was analyzed by semiquantitative polymerase chain reaction in serial blood samples obtained from 11 untreated and 11 ART-treated patients. Repertoire variations were evaluated longitudinally. Stabilization of the TCRBV repertoire was more consistently observed in treated as compared with untreated patients. Furthermore, the extent and the rapidity of stabilization were significantly different in treated versus untreated patients. TCRBV repertoire stabilization was positively correlated with the slope of HIV viremia in the treated group, suggesting an association between repertoire stabilization and virologic response to treatment. To test whether stabilization was associated with variations in the clonal complexity of T-cell populations, T-cell receptor (TCR) heteroduplex mobility shift assays (HMAs) were performed on sequential samples from 4 HAART-treated subjects. Densitometric analysis of HMA profiles showed a reduction in the number of TCR clonotypes in most TCRBV families and a significant decrease in the total number of clonotypes following 7 months of HAART. Furthermore, a biphasic decline in HIV-specific but not heterologous CTL clones was observed. This indicates that ART leads to a global reduction of CD8(+) T-cell oligoclonality and significantly modulates the mobilization of HIV-specific CTL during primary infection. (Blood. 2000;95:1743-1751)

Keywords: JOURNAL ARTICLE Acute Disease Anti-HIV Agents/*ADMINISTRATION & DOSAGE/PHARMACOLOGY Clone Cells/IMMUNOLOGY Didanosine/ADMINISTRATION & DOSAGE/PHARMACOLOGY Drug Administration Schedule Drug Therapy, Combination *Gene Rearrangement, beta-Chain T-Cell Antigen Receptor Human HIV Infections/*DRUG THERAPY/IMMUNOLOGY HIV Protease Inhibitors/ADMINISTRATION & DOSAGE/PHARMACOLOGY *HIV-1 HIV-1 Reverse Transcriptase/ANTAGONISTS & INHIB Indinavir/ADMINISTRATION & DOSAGE/PHARMACOLOGY Lamivudine/ADMINISTRATION & DOSAGE/PHARMACOLOGY *Lymphocyte Transformation Polymerase Chain Reaction RNA-Directed DNA Polymerase/ADMINISTRATION & DOSAGE/PHARMACOLOGY Saquinavir/ADMINISTRATION & DOSAGE/PHARMACOLOGY Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. T-Lymphocytes, Cytotoxic/*DRUG EFFECTS/IMMUNOLOGY Viremia/*DRUG THERAPY/IMMUNOLOGY Zidovudine/ADMINISTRATION & DOSAGE/PHARMACOLOGY

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