Immunological and virological study of enfuvirtide-treated HIV-positive patients
- 1 August 2004
- journal article
- clinical trial
- Published by Wolters Kluwer Health in AIDS
- Vol. 18 (12) , 1673-1682
- https://doi.org/10.1097/01.aids.0000131350.22032.b5
Abstract
To evaluate the predictive value and evolution of immunological and virological parameters related to HIV entry and pathogenesis in patients receiving enfuvirtide (ENF) plus an optimized regimen. A phase III clinical trial substudy of ENF in 22 patients measured virus coreceptor use and sensitivity to ENF, levels of chemokines, cytokines and chemokine receptors, CD38 and HLA-DR expression as markers of T cell activation and ex vivo cell death at baseline and at week 32. Treatment including ENF reduced HIV viral load (P < 0.001) and increased the CD4 cell count in patients that responded (RP) to treatment (n = 14). Significant (P < 0.05) increases were noted in the RP group in CXCR4 and CCR5 expression in CD4 cells without major differences in chemokine and interleukin-7 levels. A decrease in CD38 expression in the absence of HLA-DR changes was observed in CD4 cells. Apoptosis of peripheral blood mononuclear cells was significantly reduced in the RP group. Coreceptor use or ENF sensitivity of virus isolated at baseline was not associated with virus resistance or response to treatment, which appeared to be related to the activation state (HLA-DR expression) of CD4 cells at baseline. The outcome of ENF-containing treatment could not be associated with HIV coreceptor use at baseline. CD4 cell activation and viral drug resistance were the only markers of treatment response. Changes induced by ENF-containing regimen were seen in HIV coreceptor expression, including an increase in CCR5+CD4+ cells, a decrease in CD38 T cells and a concomitant reduction of T cell apoptosis.Keywords
This publication has 32 references indexed in Scilit:
- T Cell Activation Is Associated with Lower CD4+T Cell Gains in Human Immunodeficiency Virus–Infected Patients with Sustained Viral Suppression during Antiretroviral TherapyThe Journal of Infectious Diseases, 2003
- Apoptosis as an HIV strategy to escape immune attackNature Reviews Immunology, 2003
- Interleukin-7-Dependent Production of RANTES That Correlates with Human Immunodeficiency Virus Disease ProgressionJournal of Virology, 2003
- Baseline Susceptibility of Primary Human Immunodeficiency Virus Type 1 to Entry InhibitorsJournal of Virology, 2003
- The Safety, Plasma Pharmacokinetics, and Antiviral Activity of Subcutaneous Enfuvirtide (T-20), a Peptide Inhibitor of gp41-Mediated Virus Fusion, in HIV-Infected AdultsAIDS Research and Human Retroviruses, 2002
- Interleukin-7 in Plasma Correlates with CD4 T-Cell Depletion and May Be Associated with Emergence of Syncytium-Inducing Variants in Human Immunodeficiency Virus Type 1-Positive IndividualsJournal of Virology, 2001
- Inhibition of HIV-1 entry before gp41 folds into its fusion-active conformationJournal of Molecular Biology, 2000
- CHEMOKINE RECEPTORS AS HIV-1 CORECEPTORS: Roles in Viral Entry, Tropism, and DiseaseAnnual Review of Immunology, 1999
- Shorter Survival in Advanced Human Immunodeficiency Virus Type 1 Infection Is More Closely Associated with T Lymphocyte Activation than with Plasma Virus Burden or Virus Chemokine Coreceptor UsageThe Journal of Infectious Diseases, 1999
- HIV Entry and Its InhibitionPublished by Elsevier ,1998