Immunological and virological study of enfuvirtide-treated HIV-positive patients.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Retrovirology Laboratory IrsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916 Badalona, Spain.
Jordi
J
Barretina
Julià
J
Blanco
Anna
A
Bonjoch
Anuska
A
Llano
Bonaventura
B
Clotet
José A
JA
Esté
D036541:ADP-ribosyl Cyclase / Q000032:analysis; D051997:ADP-ribosyl Cyclase 1; D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000032:analysis; D018791:CD4 Lymphocyte Count; D018925:Chemokines / Q000032:analysis; D016207:Cytokines / Q000032:analysis; D024882:Drug Resistance, Viral / Q000276:immunology; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000276:immunology / Q000627:therapeutic use*; D023581:HIV Fusion Inhibitors / Q000276:immunology / Q000627:therapeutic use*; D006679:HIV Seropositivity / Q000188:drug therapy* / Q000276:immunology / Q000635:transmission; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins; D008826:Microbial Sensitivity Tests; D010446:Peptide Fragments / Q000276:immunology / Q000627:therapeutic use*; D019713:Receptors, CCR5 / Q000032:analysis; D019718:Receptors, CXCR4 / Q000032:analysis; D016896:Treatment Outcome; D019562:Viral Load
D015703:Antigens, CD; D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D000077560:Enfuvirtide; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1