Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease.

Highly active antiretroviral therapy (HAART) increases CD4(+) cell numbers, but its ability to correct the human immunodeficiency virus (HIV)-induced immune deficiency remains unknown. A three-phase T cell reconstitution was demonstrated after HAART, with: (i) an early rise of memory CD4(+) cells, (ii) a reduction in T cell activation correlated to the decreasing retroviral activity together with an improved CD4(+) T cell reactivity to recall antigens, and (iii) a late rise of "naïve" CD4(+) lymphocytes while CD8(+) T cells declined, however, without complete normalization of these parameters. Thus, decreasing the HIV load can reverse HIV-driven activation and CD4(+) T cell defects in advanced HIV-infected patients.

[1]  D. Cooper,et al.  Alterations in the immune response of human immunodeficiency virus (HIV)-infected subjects treated with an HIV-specific protease inhibitor, ritonavir. , 1996, The Journal of infectious diseases.

[2]  J. Sprent Lifespans of naive, memory and effector lymphocytes. , 1993, Current opinion in immunology.

[3]  J. Giorgi Phenotype and Function of T Cells in HIV Disease , 1996 .

[4]  J. Pocidalo,et al.  The significance of activation markers on CD8 lymphocytes in human immunodeficiency syndrome: staging and prognostic value , 1992, Clinical and experimental immunology.

[5]  G S Kansas,et al.  Selectins and their ligands: current concepts and controversies. , 1996, Blood.

[6]  D. Ho,et al.  A preliminary study of ritonavir, an inhibitor of HIV-1 protease, to treat HIV-1 infection. , 1995, The New England journal of medicine.

[7]  T. Merigan,et al.  Treatment of human immunodeficiency virus infection with saquinavir, zidovudine, and zalcitabine. AIDS Clinical Trials Group. , 1996, The New England journal of medicine.

[8]  B. Rocha,et al.  Peripheral selection of the T cell repertoire. , 1991, Science.

[9]  Niels Schaft,et al.  T Cell Telomere Length in HIV-1 Infection: No Evidence for Increased CD4+ T Cell Turnover , 1996, Science.

[10]  J V Giorgi,et al.  Early effects of HIV on CD4 lymphocytes in vivo. , 1987, Journal of immunology.

[11]  M. Cooper,et al.  Human lymphocyte differentiation antigens HB-10 and HB-11. II. Differential production of B cell growth and differentiation factors by distinct helper T cell subpopulations. , 1985, Journal of immunology.

[12]  S. Steinberg,et al.  Age, thymopoiesis, and CD4+ T-lymphocyte regeneration after intensive chemotherapy. , 1995, The New England journal of medicine.

[13]  C. Harley,et al.  Shortened telomeres in the expanded CD28-CD8+ cell subset in HIV disease implicate replicative senescence in HIV pathogenesis. , 1996, AIDS.

[14]  R. Schinazi,et al.  Infectious amplification of wild-type human immunodeficiency virus from patients' lymphocytes and modulation by reverse transcriptase inhibitors in vitro , 1993, Antimicrobial Agents and Chemotherapy.

[15]  Jaap,et al.  Immunological abnormalities in human immunodeficiency virus (HIV)-infected asymptomatic homosexual men. HIV affects the immune system before CD4+ T helper cell depletion occurs. , 1988, The Journal of clinical investigation.

[16]  J. Justement,et al.  Preferential infection of CD4+ memory T cells by human immunodeficiency virus type 1: evidence for a role in the selective T-cell functional defects observed in infected individuals. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[17]  C. Sabin,et al.  Increased numbers of primed activated CD8+CD38+CD45RO+ T cells predict the decline of CD4+ T cells in HIV-1-infected patients. , 1996, AIDS.

[18]  B. Autran,et al.  A Th0/Th2-like function of CD4+CD7- T helper cells from normal donors and HIV-infected patients. , 1995, Journal of immunology.

[19]  M. Roederer,et al.  CD8 naive T cell counts decrease progressively in HIV-infected adults. , 1995, The Journal of clinical investigation.

[20]  B. Rocha,et al.  The peripheral T cell repertoire: independent homeostatic regulation of virgin and activated CD8+ T cell pools , 1995, European journal of immunology.

[21]  L. Terry,et al.  Limiting dilution analysis of proliferative responses in human lymphocyte populations defined by the monoclonal antibody UCHL1: implications for differential CD45 expression in T cell memory formation , 1988, European journal of immunology.

[22]  T. Waldmann,et al.  Qualitative analysis of immune function in patients with the acquired immunodeficiency syndrome. Evidence for a selective defect in soluble antigen recognition. , 1985, The New England journal of medicine.

[23]  J. Sprent,et al.  Viruses and T Cell Turnover: Evidence for Bystander Proliferation , 1996, Immunological reviews.

[24]  M. Johnson,et al.  Lymphocyte activation in HIV‐1 infection. II. Functional defects of CD28− T cells , 1994, AIDS.

[25]  M. Zupancic,et al.  Kinetics of response in lymphoid tissues to antiretroviral therapy of HIV-1 infection. , 1997, Science.

[26]  Martin A. Nowak,et al.  Viral dynamics in human immunodeficiency virus type 1 infection , 1995, Nature.

[27]  S. Fu,et al.  Human T cell activation. III. Rapid induction of a phosphorylated 28 kD/32 kD disulfide-linked early activation antigen (EA 1) by 12-o- tetradecanoyl phorbol-13-acetate, mitogens, and antigens , 1986, The Journal of experimental medicine.

[28]  J. Giorgi,et al.  Immunology of HIV infection. , 1990, International reviews of immunology.