Long-term Kinetics of T Cell Production in HIV-infected Subjects Treated with Highly Active Antiretroviral Therapy

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2000 May 11

PMID 10805798

Citations 25

Authors

S Fleury

G P Rizzardi

A Chapuis

G Tambussi

C Knabenhans

E Simeoni

J Y Meuwly

J M Corpataux

A Lazzarin

F Miedema

G Pantaleo

Affiliations

Soon will be listed here.

Abstract

The long-term kinetics of T cell production following highly active antiretroviral therapy (HAART) were investigated in blood and lymph node in a group of HIV-infected subjects at early stage of established infection and prospectively studied for 72 wk. Before HAART, CD4 and CD8 T cell turnover was increased. However, the total number of proliferating CD4(+) T lymphocytes, i.e., CD4(+)Ki67(+) T lymphocytes, was not significantly different in HIV-infected (n = 73) and HIV-negative (n = 15) subjects, whereas proliferating CD8(+)Ki67(+) T lymphocytes were significantly higher in HIV-infected subjects. After HAART, the total body number of proliferating CD4(+)Ki67(+) T lymphocytes increased over time and was associated with an increase of both naive and memory CD4(+) T cells. The maximal increase (2-fold) was observed at week 36, whereas at week 72 the number of proliferating CD4(+) T cells dropped to baseline levels, i.e., before HAART. The kinetics of the fraction of proliferating CD4 and CD8 T cells were significantly correlated with the changes in the total body number of these T cell subsets. These results demonstrate a direct relationship between ex vivo measures of T cell production and quantitative changes in total body T lymphocyte populations. This study provides advances in the delineation of the kinetics of T cell production in HIV infection in the presence and/or in the absence of HAART.

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References

Autran B, Carcelain G, Li T, Blanc C, Mathez D, Tubiana R . Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease. Science. 1997; 277(5322):112-6. DOI: 10.1126/science.277.5322.112. View

Havlir D, Marschner I, Hirsch M, Collier A, Tebas P, Bassett R . Maintenance antiretroviral therapies in HIV-infected subjects with undetectable plasma HIV RNA after triple-drug therapy. AIDS Clinical Trials Group Study 343 Team. N Engl J Med. 1998; 339(18):1261-8. DOI: 10.1056/NEJM199810293391801. View

Gulick R, Mellors J, Havlir D, Eron J, Gonzalez C, McMahon D . Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy. N Engl J Med. 1997; 337(11):734-9. DOI: 10.1056/NEJM199709113371102. View

Rosenberg E, Billingsley J, Caliendo A, Boswell S, Sax P, Kalams S . Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia. Science. 1997; 278(5342):1447-50. DOI: 10.1126/science.278.5342.1447. View

Hellerstein M, McCune J . T cell turnover in HIV-1 disease. Immunity. 1997; 7(5):583-9. DOI: 10.1016/s1074-7613(00)80379-9. View

Goh W, Rogel M, Kinsey C, Michael S, Fultz P, Nowak M . HIV-1 Vpr increases viral expression by manipulation of the cell cycle: a mechanism for selection of Vpr in vivo. Nat Med. 1998; 4(1):65-71. DOI: 10.1038/nm0198-065. View

Mohri H, Bonhoeffer S, Monard S, Perelson A, Ho D . Rapid turnover of T lymphocytes in SIV-infected rhesus macaques. Science. 1998; 279(5354):1223-7. DOI: 10.1126/science.279.5354.1223. View

Altman J, Suresh M, Sourdive D, Zajac A, Miller J, Slansky J . Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection. Immunity. 1998; 8(2):177-87. DOI: 10.1016/s1074-7613(00)80470-7. View

Ogg G, Jin X, Bonhoeffer S, Dunbar P, Nowak M, Monard S . Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA. Science. 1998; 279(5359):2103-6. DOI: 10.1126/science.279.5359.2103. View

10.

Sachsenberg N, Perelson A, Yerly S, Schockmel G, Leduc D, Hirschel B . Turnover of CD4+ and CD8+ T lymphocytes in HIV-1 infection as measured by Ki-67 antigen. J Exp Med. 1998; 187(8):1295-303. PMC: 2212238. DOI: 10.1084/jem.187.8.1295. View

11.

McMichael A, OCallaghan C . A new look at T cells. J Exp Med. 1998; 187(9):1367-71. PMC: 2212275. DOI: 10.1084/jem.187.9.1367. View

12.

Tissot O, Viard J, Rabian C, Ngo N, Burgard M, Rouzioux C . No evidence for proliferation in the blood CD4+ T-cell pool during HIV-1 infection and triple combination therapy. AIDS. 1998; 12(8):879-84. DOI: 10.1097/00002030-199808000-00010. View

13.

Fleury S, de Boer R, Rizzardi G, Wolthers K, Otto S, Welbon C . Limited CD4+ T-cell renewal in early HIV-1 infection: effect of highly active antiretroviral therapy. Nat Med. 1998; 4(7):794-801. DOI: 10.1038/nm0798-794. View

14.

Komanduri K, Viswanathan M, Wieder E, Schmidt D, Bredt B, Jacobson M . Restoration of cytomegalovirus-specific CD4+ T-lymphocyte responses after ganciclovir and highly active antiretroviral therapy in individuals infected with HIV-1. Nat Med. 1998; 4(8):953-6. DOI: 10.1038/nm0898-953. View

15.

Li T, Tubiana R, Katlama C, Calvez V, Ait Mohand H, Autran B . Long-lasting recovery in CD4 T-cell function and viral-load reduction after highly active antiretroviral therapy in advanced HIV-1 disease. Lancet. 1998; 351(9117):1682-6. DOI: 10.1016/s0140-6736(97)10291-4. View

16.

Pialoux G, Raffi F, Brun-Vezinet F, Meiffredy V, Flandre P, Gastaut J . A randomized trial of three maintenance regimens given after three months of induction therapy with zidovudine, lamivudine, and indinavir in previously untreated HIV-1-infected patients. Trilège (Agence Nationale de Recherches sur le SIDA 072) Study.... N Engl J Med. 1998; 339(18):1269-76. DOI: 10.1056/NEJM199810293391802. View

17.

Michelet C, Arvieux C, Francois C, Besnier J, Rogez J, Breux J . Opportunistic infections occurring during highly active antiretroviral treatment. AIDS. 1998; 12(14):1815-22. DOI: 10.1097/00002030-199814000-00013. View

18.

Douek D, McFarland R, KEISER P, Gage E, Massey J, Haynes B . Changes in thymic function with age and during the treatment of HIV infection. Nature. 1999; 396(6712):690-5. DOI: 10.1038/25374. View

19.

Pantaleo G . Unraveling the strands of HIV's web. Nat Med. 1999; 5(1):27-8. DOI: 10.1038/4706. View

20.

BRODIE S, Lewinsohn D, Patterson B, Jiyamapa D, Krieger J, Corey L . In vivo migration and function of transferred HIV-1-specific cytotoxic T cells. Nat Med. 1999; 5(1):34-41. DOI: 10.1038/4716. View