The independent effect of drug resistance on T cell activation in HIV infection

Peter W. Hunt, Steven G. Deeks, David Bangsberg, Andrew Moss, Elizabeth Sinclair, Teri Liegler, Michael Bates, Gabriel Tsao, Harry Lampiris, Rebecca Hoh, Jeffrey N. Martin

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

OBJECTIVE: Antiretroviral-treated individuals with drug-resistant HIV experience slower CD4 cell count declines than untreated individuals, independent of degree of viremia. As immune activation independently predicts disease progression, we hypothesized that patients with drug-resistant viremia would have less immune activation than patients with wild-type viremia, independent of plasma HIV RNA levels and that these differences would not be explained by a direct drug effect of protease inhibitors. METHODS: Percentages of activated (CD38/HLA-DR) T cells were compared between untreated participants with wild-type viremia and antiretroviral-treated participants with drug-resistant viremia, after adjusting for plasma HIV RNA levels among other factors associated with T cell activation. Changes in T cell activation were also assessed in subjects discontinuing protease inhibitors while continuing other antiretroviral medications. RESULTS: Twenty-one untreated participants with wild-type viremia and 70 antiretroviral-treated participants with drug-resistant viremia were evaluated. Relative to untreated participants, those with drug-resistant viremia had 29% fewer activated CD4 (P = 0.051) and CD8 (P = 0.012) T cells after adjustment for plasma HIV RNA levels among other factors. There was no evidence for an early change in T cell activation among 13 subjects with drug-resistant viremia interrupting protease inhibitors while continuing other antiretroviral medications, but a significant increase in T cell activation with complete or partial emergence of wild-type sequences in protease. CONCLUSIONS: Antiretroviral-treated patients with drug-resistant viremia have less T cell activation than untreated patients, independent of plasma HIV RNA level. Decreased ability of drug-resistant variants to cause T cell activation likely contributes to slower CD4 cell count declines among patients with drug-resistant viremia.

Original languageEnglish (US)
Pages (from-to)691-699
Number of pages9
JournalAIDS
Volume20
Issue number5
DOIs
StatePublished - 2006
Externally publishedYes

Fingerprint

Viremia
Drug Resistance
HIV Infections
T-Lymphocytes
Pharmaceutical Preparations
HIV
Protease Inhibitors
RNA
CD4 Lymphocyte Count
HLA-DR Antigens
Disease Progression
Peptide Hydrolases

Keywords

  • Antiretroviral therapy
  • Drug resistance
  • HIV
  • T cell activation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Hunt, P. W., Deeks, S. G., Bangsberg, D., Moss, A., Sinclair, E., Liegler, T., ... Martin, J. N. (2006). The independent effect of drug resistance on T cell activation in HIV infection. AIDS, 20(5), 691-699. https://doi.org/10.1097/01.aids.0000216369.30948.18

The independent effect of drug resistance on T cell activation in HIV infection. / Hunt, Peter W.; Deeks, Steven G.; Bangsberg, David; Moss, Andrew; Sinclair, Elizabeth; Liegler, Teri; Bates, Michael; Tsao, Gabriel; Lampiris, Harry; Hoh, Rebecca; Martin, Jeffrey N.

In: AIDS, Vol. 20, No. 5, 2006, p. 691-699.

Research output: Contribution to journalArticle

Hunt, PW, Deeks, SG, Bangsberg, D, Moss, A, Sinclair, E, Liegler, T, Bates, M, Tsao, G, Lampiris, H, Hoh, R & Martin, JN 2006, 'The independent effect of drug resistance on T cell activation in HIV infection', AIDS, vol. 20, no. 5, pp. 691-699. https://doi.org/10.1097/01.aids.0000216369.30948.18
Hunt, Peter W. ; Deeks, Steven G. ; Bangsberg, David ; Moss, Andrew ; Sinclair, Elizabeth ; Liegler, Teri ; Bates, Michael ; Tsao, Gabriel ; Lampiris, Harry ; Hoh, Rebecca ; Martin, Jeffrey N. / The independent effect of drug resistance on T cell activation in HIV infection. In: AIDS. 2006 ; Vol. 20, No. 5. pp. 691-699.
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AU - Bangsberg, David

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AU - Liegler, Teri

AU - Bates, Michael

AU - Tsao, Gabriel

AU - Lampiris, Harry

AU - Hoh, Rebecca

AU - Martin, Jeffrey N.

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N2 - OBJECTIVE: Antiretroviral-treated individuals with drug-resistant HIV experience slower CD4 cell count declines than untreated individuals, independent of degree of viremia. As immune activation independently predicts disease progression, we hypothesized that patients with drug-resistant viremia would have less immune activation than patients with wild-type viremia, independent of plasma HIV RNA levels and that these differences would not be explained by a direct drug effect of protease inhibitors. METHODS: Percentages of activated (CD38/HLA-DR) T cells were compared between untreated participants with wild-type viremia and antiretroviral-treated participants with drug-resistant viremia, after adjusting for plasma HIV RNA levels among other factors associated with T cell activation. Changes in T cell activation were also assessed in subjects discontinuing protease inhibitors while continuing other antiretroviral medications. RESULTS: Twenty-one untreated participants with wild-type viremia and 70 antiretroviral-treated participants with drug-resistant viremia were evaluated. Relative to untreated participants, those with drug-resistant viremia had 29% fewer activated CD4 (P = 0.051) and CD8 (P = 0.012) T cells after adjustment for plasma HIV RNA levels among other factors. There was no evidence for an early change in T cell activation among 13 subjects with drug-resistant viremia interrupting protease inhibitors while continuing other antiretroviral medications, but a significant increase in T cell activation with complete or partial emergence of wild-type sequences in protease. CONCLUSIONS: Antiretroviral-treated patients with drug-resistant viremia have less T cell activation than untreated patients, independent of plasma HIV RNA level. Decreased ability of drug-resistant variants to cause T cell activation likely contributes to slower CD4 cell count declines among patients with drug-resistant viremia.

AB - OBJECTIVE: Antiretroviral-treated individuals with drug-resistant HIV experience slower CD4 cell count declines than untreated individuals, independent of degree of viremia. As immune activation independently predicts disease progression, we hypothesized that patients with drug-resistant viremia would have less immune activation than patients with wild-type viremia, independent of plasma HIV RNA levels and that these differences would not be explained by a direct drug effect of protease inhibitors. METHODS: Percentages of activated (CD38/HLA-DR) T cells were compared between untreated participants with wild-type viremia and antiretroviral-treated participants with drug-resistant viremia, after adjusting for plasma HIV RNA levels among other factors associated with T cell activation. Changes in T cell activation were also assessed in subjects discontinuing protease inhibitors while continuing other antiretroviral medications. RESULTS: Twenty-one untreated participants with wild-type viremia and 70 antiretroviral-treated participants with drug-resistant viremia were evaluated. Relative to untreated participants, those with drug-resistant viremia had 29% fewer activated CD4 (P = 0.051) and CD8 (P = 0.012) T cells after adjustment for plasma HIV RNA levels among other factors. There was no evidence for an early change in T cell activation among 13 subjects with drug-resistant viremia interrupting protease inhibitors while continuing other antiretroviral medications, but a significant increase in T cell activation with complete or partial emergence of wild-type sequences in protease. CONCLUSIONS: Antiretroviral-treated patients with drug-resistant viremia have less T cell activation than untreated patients, independent of plasma HIV RNA level. Decreased ability of drug-resistant variants to cause T cell activation likely contributes to slower CD4 cell count declines among patients with drug-resistant viremia.

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