Reduction in T cell apoptosis in patients with HIV disease following antiretroviral therapy

Surendra J. Chavan; Seetha L. Tamma; Mark Kaplan; Merril Gersten; Savita G. Pahwa

doi:10.1006/clim.1999.4770

Reduction in T cell apoptosis in patients with HIV disease following antiretroviral therapy

Surendra J. Chavan, Seetha L. Tamma, Mark Kaplan, Merril Gersten, Savita G. Pahwa

Research output: Contribution to journal › Article › peer-review

38 Scopus citations

Abstract

Patients with HIV infection manifest increased T lymphocyte apoptosis. This study investigated the influence of antiretroviral therapy (ART) upon lymphocyte apoptosis in 23 HIV-infected adults naive to protease inhibitors. Patients were enrolled in a treatment trial consisting of Nelfinavir (NFV), d4T, or NFV + d4T for 24 weeks, followed by triple therapy (NFV + reverse transcriptase inhibitors) for an additional 24 weeks. Spontaneous T cell apoptosis in cultured PBMC decreased by 23.67 ± 18.2% (P < 0.006) at 48 weeks and plasma HIV RNA decreased by 1.79 ± 0.59 log₁₀ RNA copies/ml (P < 0.001). The absolute decrease and slope of T cell apoptosis correlated with plasma virus load and with activated CD8 T cells and was inversely correlated with CD4 T cells. We conclude that reduction in chronic antigenic stimulation and the absence of cellular signals elicited by viral products contribute to the rescue of T lymphocytes from apoptosis, which facilitates immunologic recovery in ART-treated patients.

Original language	English (US)
Pages (from-to)	24-33
Number of pages	10
Journal	Clinical Immunology
Volume	93
Issue number	1
DOIs	https://doi.org/10.1006/clim.1999.4770
State	Published - Oct 1999
Externally published	Yes

Keywords

Apoptosis
FACS
HIV/AIDS
Human
T-lymphocytes

ASJC Scopus subject areas

Immunology
Immunology and Allergy
Pathology and Forensic Medicine

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title = "Reduction in T cell apoptosis in patients with HIV disease following antiretroviral therapy",

abstract = "Patients with HIV infection manifest increased T lymphocyte apoptosis. This study investigated the influence of antiretroviral therapy (ART) upon lymphocyte apoptosis in 23 HIV-infected adults naive to protease inhibitors. Patients were enrolled in a treatment trial consisting of Nelfinavir (NFV), d4T, or NFV + d4T for 24 weeks, followed by triple therapy (NFV + reverse transcriptase inhibitors) for an additional 24 weeks. Spontaneous T cell apoptosis in cultured PBMC decreased by 23.67 ± 18.2% (P < 0.006) at 48 weeks and plasma HIV RNA decreased by 1.79 ± 0.59 log10 RNA copies/ml (P < 0.001). The absolute decrease and slope of T cell apoptosis correlated with plasma virus load and with activated CD8 T cells and was inversely correlated with CD4 T cells. We conclude that reduction in chronic antigenic stimulation and the absence of cellular signals elicited by viral products contribute to the rescue of T lymphocytes from apoptosis, which facilitates immunologic recovery in ART-treated patients.",

keywords = "Apoptosis, FACS, HIV/AIDS, Human, T-lymphocytes",

author = "Chavan, {Surendra J.} and Tamma, {Seetha L.} and Mark Kaplan and Merril Gersten and Pahwa, {Savita G.}",

note = "Funding Information: This paper was presented in part at the 12th World AIDS Conference, Geneva, June 1998 (Abstract No. 21163). Informed consent was obtained from all patients and human experimentation guidelines of the U.S. Department of Health and Human Services were followed. Financial support was provided by Grants AI 28281 and DA05161 from the National Institutes of Health, Bethesda, MD. We thank Dr. Thomas W. McCloskey for helpful discussions. We are indebted to Regina Kowalski and Maria Marecki for technical assistance. We thank Agouron Pharmaceuticals for providing the plasma HIV RNA data.",

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AU - Kaplan, Mark

AU - Gersten, Merril

AU - Pahwa, Savita G.

N1 - Funding Information: This paper was presented in part at the 12th World AIDS Conference, Geneva, June 1998 (Abstract No. 21163). Informed consent was obtained from all patients and human experimentation guidelines of the U.S. Department of Health and Human Services were followed. Financial support was provided by Grants AI 28281 and DA05161 from the National Institutes of Health, Bethesda, MD. We thank Dr. Thomas W. McCloskey for helpful discussions. We are indebted to Regina Kowalski and Maria Marecki for technical assistance. We thank Agouron Pharmaceuticals for providing the plasma HIV RNA data.

PY - 1999/10

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N2 - Patients with HIV infection manifest increased T lymphocyte apoptosis. This study investigated the influence of antiretroviral therapy (ART) upon lymphocyte apoptosis in 23 HIV-infected adults naive to protease inhibitors. Patients were enrolled in a treatment trial consisting of Nelfinavir (NFV), d4T, or NFV + d4T for 24 weeks, followed by triple therapy (NFV + reverse transcriptase inhibitors) for an additional 24 weeks. Spontaneous T cell apoptosis in cultured PBMC decreased by 23.67 ± 18.2% (P < 0.006) at 48 weeks and plasma HIV RNA decreased by 1.79 ± 0.59 log10 RNA copies/ml (P < 0.001). The absolute decrease and slope of T cell apoptosis correlated with plasma virus load and with activated CD8 T cells and was inversely correlated with CD4 T cells. We conclude that reduction in chronic antigenic stimulation and the absence of cellular signals elicited by viral products contribute to the rescue of T lymphocytes from apoptosis, which facilitates immunologic recovery in ART-treated patients.

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