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Science 4 July 1997:
Vol. 277. no. 5322, pp. 112 - 116
DOI: 10.1126/science.277.5322.112
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Reports

Positive Effects of Combined Antiretroviral Therapy on CD4+ T Cell Homeostasis and Function in Advanced HIV Disease

B. Autran, * G. Carcelain, T. S. Li, dagger C. Blanc, dagger D. Mathez, R. Tubiana, C. Katlama, P. Debré, J. Leibowitch

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.

B. Autran, G. Carcelain, T. S. Li, C. Blanc, P. Debré, Laboratoire d'Immunologie Cellulaire, URA CNRS 625, Hôpital Pitié-Salpétriêre, 47-83 Boulevard de l'Hôpital, Paris, France.
D. Mathez and J. Leibowitch, Service d'Immunologie Hématologie, Hôpital Raymond Poincaré, Garches, France.
R. Tubiana and C. Katlama, Service de Maladies Infectieuses et Tropicales, Hôpital Pitié-Salpétriêre, Paris, France.
*   To whom correspondence should be addressed. E-mail: autran{at}psl.ap-hop-paris.fr

dagger    These authors contributed equally to this work.

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Effects of Prostratin on T-Cell Activation and Human Immunodeficiency Virus Latency.
Y. D. Korin, D. G. Brooks, S. Brown, A. Korotzer, and J. A. Zack (2002)
J. Virol. 76, 8118-8123
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T-cell repopulation and thymic volume in HIV-1-infected adult patients after highly active antiretroviral therapy.
J. M. Franco, A. Rubio, M. Martinez-Moya, M. Leal, E. Merchante, A. Sanchez-Quijano, and E. Lissen (2002)
Blood 99, 3702-3706
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Discordance between Frequency of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Gamma Interferon-Producing CD4+ T Cells and HIV-1-Specific Lymphoproliferation in HIV-1-Infected Subjects with Active Viral Replication.
B. E. Palmer, E. Boritz, N. Blyveis, and C. C. Wilson (2002)
J. Virol. 76, 5925-5936
   Abstract »    Full Text »    PDF »
Interferon-{alpha} as an immunotherapeutic protein.
D. L. Brassard, M. J. Grace, and R. W. Bordens (2002)
J. Leukoc. Biol. 71, 565-581
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Selective granulocyte/monocyte apheresis in the treatment of HIV-infected patients: short-term and long-term effects on immunological and virological parameters.
A. Beretta, H. Hasson, A. Samiabadi, M. Alfano, D. Trabattoni, F. Lillo, P. Ferrante, M. Clerici, and A. Lazzarin (2002)
Perfusion 17, 47-51
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Human Immunodeficiency Virus Type 1-Hepatitis C Virus Coinfection: Intraindividual Comparison of Cellular Immune Responses against Two Persistent Viruses.
G. M. Lauer, T. N. Nguyen, C. L. Day, G. K. Robbins, T. Flynn, K. McGowan, E. S. Rosenberg, M. Lucas, P. Klenerman, R. T. Chung, et al. (2002)
J. Virol. 76, 2817-2826
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Effectiveness of highly active antiretroviral therapy among HIV-1 infected women.
S J Gange, Y Barron, R M Greenblatt, K Anastos, H Minkoff, M Young, A Kovacs, M Cohen, W A Meyer III, and A Munoz (2002)
J Epidemiol Community Health 56, 153-159
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Immune reconstitution eosinophilia due to schistosomiasis.
R Fernando and R Miller (2002)
Sex Transm Inf 78, 76
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Residual Viral Replication during Antiretroviral Therapy Boosts Human Immunodeficiency Virus Type 1-Specific CD8+ T-Cell Responses in Subjects Treated Early after Infection.
G. M. Ortiz, J. Hu, J. A. Goldwitz, R. Chandwani, M. Larsson, N. Bhardwaj, S. Bonhoeffer, B. Ramratnam, L. Zhang, M. M. Markowitz, et al. (2002)
J. Virol. 76, 411-415
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Structured Treatment Interruptions for the Management of HIV Infection.
F. Lori and J. Lisziewicz (2001)
JAMA 286, 2981-2987
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Pulmonary Complications of HIV Infection . Report of the Fourth NHLBI Workshop.
J. M. BECK, M. J. ROSEN, and H. H. PEAVY (2001)
Am. J. Respir. Crit. Care Med. 164, 2120-2126
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Non-Hodgkin lymphoma in HIV-infected patients in the era of highly active antiretroviral therapy.
O. Kirk, C. Pedersen, A. Cozzi-Lepri, F. Antunes, V. Miller, J. M. Gatell, C. Katlama, A. Lazzarin, P. Skinhoj, and S. E. Barton (2001)
Blood 98, 3406-3412
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High-level HIV-1 viremia suppresses viral antigen-specific CD4+ T cell proliferation.
A. C. McNeil, W. L. Shupert, C. A. Iyasere, C. W. Hallahan, J. Mican, R. T. Davey Jr., and M. Connors (2001)
PNAS 98, 13878-13883
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Reduced blood CD123+ (lymphoid) and CD11c+ (myeloid) dendritic cell numbers in primary HIV-1 infection.
J. Pacanowski, S. Kahi, M. Baillet, P. Lebon, C. Deveau, C. Goujard, L. Meyer, E. Oksenhendler, M. Sinet, and A. Hosmalin (2001)
Blood 98, 3016-3021
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Neutralizing Antibodies Associated with Viremia Control in a Subset of Individuals after Treatment of Acute Human Immunodeficiency Virus Type 1 Infection.
D. C. Montefiori, T. S. Hill, H. T. T. Vo, B. D. Walker, and E. S. Rosenberg (2001)
J. Virol. 75, 10200-10207
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Enhancement of Innate Immunity against Mycobacterium avium Infection by Immunostimulatory DNA Is Mediated by Indoleamine 2,3-Dioxygenase.
T. Hayashi, S. P. Rao, K. Takabayashi, J. H. Van Uden, R. S. Kornbluth, S. M. Baird, M. W. Taylor, D. A. Carson, A. Catanzaro, and E. Raz (2001)
Infect. Immun. 69, 6156-6164
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Highly Active Antiretroviral Therapy in Human Immunodeficiency Virus Type 1-Infected Children: Analysis of Cellular Immune Responses.
V. Blazevic, S. Jankelevich, S. M. Steinberg, F. Jacobsen, R. Yarchoan, and G. M. Shearer (2001)
Clin. Vaccine Immunol. 8, 943-948
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Immune interventions: The changing face of HIV and AIDS.
J. Wilkinson and F. Gotch (2001)
Br. Med. Bull. 58, 187-203
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T Cell Homeostasis: Thymus Regeneration and Peripheral T Cell Restoration in Mice with a Reduced Fraction of Competent Precursors.
A. R.M. Almeida, J. A.M. Borghans, and A. A. Freitas (2001)
J. Exp. Med. 194, 591-600
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Antiapoptotic mechanism of HIV protease inhibitors: preventing mitochondrial transmembrane potential loss.
B. N. Phenix, J. J. Lum, Z. Nie, J. Sanchez-Dardon, and A. D. Badley (2001)
Blood 98, 1078-1085
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In Vitro Hydroxyurea Decreases Th1 Cell-Mediated Immunity.
A. Weinberg (2001)
Clin. Vaccine Immunol. 8, 702-705
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Neutralizing Antibodies against Autologous Human Immunodeficiency Virus Type 1 Isolates in Patients with Increasing CD4 Cell Counts despite Incomplete Virus Suppression during Antiretroviral Treatment.
L. Sarmati, G. d'Ettorre, E. Nicastri, L. Ercoli, I. Uccella, P. Massetti, S. G. Parisi, V. Vullo, and M. Andreoni (2001)
Clin. Vaccine Immunol. 8, 822-824
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CMVR diagnoses and progression of CD4 cell counts and HIV viral load measurements in HIV patients on HAART.
H. J Zambarakji, R. B Newson, and S. M Mitchell (2001)
Br. J. Ophthalmol. 85, 837-841
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AIDS and the lung in a changing world.
C MAYAUD and J CADRANEL (2001)
Thorax 56, 423-426
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