A randomized, controlled trial of raltegravir intensification in antiretroviral-treated, HIV-infected patients with a suboptimal CD4+ T cell response

Hiroyu Hatano, Timothy L. Hayes, Viktor Dahl, Elizabeth Sinclair, Tzong Hae Lee, Rebecca Hoh, Harry Lampiris, Peter W. Hunt, Sarah Palmer, Joseph M. McCune, Jeffrey N. Martin, Michael P. Busch, Barbara Shacklett, Steven G. Deeks

Research output: Contribution to journalArticle

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Abstract

Background. Some human immunodeficiency virus (HIV)-infected individuals are not able to achieve a normal CD4+ T cell count despite prolonged, treatment-mediated viral suppression. We conducted an intensification study to assess whether residual viral replication contributes to replenishment of the latent reservoir and whether mucosal HIV-specific T cell responses limit the reservoir size. Methods. Thirty treated subjects with CD4+ T cell counts of <350 cells/mm3 despite viral suppression for ≥1 year were randomized to add raltegravir (400 mg twice daily) or matching placebo for 24 weeks. The primary end points were the proportion of subjects with undetectable plasma viremia (determined using an ultrasensitive assay with a lower limit of detection of <.3 copy/mL) and a change in the percentage of CD38+HLA-DR+CD8+ T cells in peripheral blood mononuclear cells (PBMCs). Results. The proportion of subjects with undetectable plasma viremia did not differ between the 2 groups (P = .42). Raltegravir intensification did not have a significant effect on immune activation or HIV-specific responses in PBMCs or gut-associated lymphoid tissue. Conclusions. Low-level viremia is not likely to be a significant cause of suboptimal CD4 + T cell gains during HIV treatment. Clinical Trials Registration. NCT00631449.

Original languageEnglish (US)
Pages (from-to)960-968
Number of pages9
JournalJournal of Infectious Diseases
Volume203
Issue number7
DOIs
StatePublished - Apr 1 2011

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Randomized Controlled Trials
HIV
Viremia
T-Lymphocytes
CD4 Lymphocyte Count
Blood Cells
Lymphoid Tissue
HLA-DR Antigens
Limit of Detection
Placebos
Raltegravir Potassium
Clinical Trials
Therapeutics

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

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A randomized, controlled trial of raltegravir intensification in antiretroviral-treated, HIV-infected patients with a suboptimal CD4+ T cell response. / Hatano, Hiroyu; Hayes, Timothy L.; Dahl, Viktor; Sinclair, Elizabeth; Lee, Tzong Hae; Hoh, Rebecca; Lampiris, Harry; Hunt, Peter W.; Palmer, Sarah; McCune, Joseph M.; Martin, Jeffrey N.; Busch, Michael P.; Shacklett, Barbara; Deeks, Steven G.

In: Journal of Infectious Diseases, Vol. 203, No. 7, 01.04.2011, p. 960-968.

Research output: Contribution to journalArticle

Hatano, H, Hayes, TL, Dahl, V, Sinclair, E, Lee, TH, Hoh, R, Lampiris, H, Hunt, PW, Palmer, S, McCune, JM, Martin, JN, Busch, MP, Shacklett, B & Deeks, SG 2011, 'A randomized, controlled trial of raltegravir intensification in antiretroviral-treated, HIV-infected patients with a suboptimal CD4+ T cell response', Journal of Infectious Diseases, vol. 203, no. 7, pp. 960-968. https://doi.org/10.1093/infdis/jiq138
Hatano, Hiroyu ; Hayes, Timothy L. ; Dahl, Viktor ; Sinclair, Elizabeth ; Lee, Tzong Hae ; Hoh, Rebecca ; Lampiris, Harry ; Hunt, Peter W. ; Palmer, Sarah ; McCune, Joseph M. ; Martin, Jeffrey N. ; Busch, Michael P. ; Shacklett, Barbara ; Deeks, Steven G. / A randomized, controlled trial of raltegravir intensification in antiretroviral-treated, HIV-infected patients with a suboptimal CD4+ T cell response. In: Journal of Infectious Diseases. 2011 ; Vol. 203, No. 7. pp. 960-968.
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AU - Dahl, Viktor

AU - Sinclair, Elizabeth

AU - Lee, Tzong Hae

AU - Hoh, Rebecca

AU - Lampiris, Harry

AU - Hunt, Peter W.

AU - Palmer, Sarah

AU - McCune, Joseph M.

AU - Martin, Jeffrey N.

AU - Busch, Michael P.

AU - Shacklett, Barbara

AU - Deeks, Steven G.

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N2 - Background. Some human immunodeficiency virus (HIV)-infected individuals are not able to achieve a normal CD4+ T cell count despite prolonged, treatment-mediated viral suppression. We conducted an intensification study to assess whether residual viral replication contributes to replenishment of the latent reservoir and whether mucosal HIV-specific T cell responses limit the reservoir size. Methods. Thirty treated subjects with CD4+ T cell counts of <350 cells/mm3 despite viral suppression for ≥1 year were randomized to add raltegravir (400 mg twice daily) or matching placebo for 24 weeks. The primary end points were the proportion of subjects with undetectable plasma viremia (determined using an ultrasensitive assay with a lower limit of detection of <.3 copy/mL) and a change in the percentage of CD38+HLA-DR+CD8+ T cells in peripheral blood mononuclear cells (PBMCs). Results. The proportion of subjects with undetectable plasma viremia did not differ between the 2 groups (P = .42). Raltegravir intensification did not have a significant effect on immune activation or HIV-specific responses in PBMCs or gut-associated lymphoid tissue. Conclusions. Low-level viremia is not likely to be a significant cause of suboptimal CD4 + T cell gains during HIV treatment. Clinical Trials Registration. NCT00631449.

AB - Background. Some human immunodeficiency virus (HIV)-infected individuals are not able to achieve a normal CD4+ T cell count despite prolonged, treatment-mediated viral suppression. We conducted an intensification study to assess whether residual viral replication contributes to replenishment of the latent reservoir and whether mucosal HIV-specific T cell responses limit the reservoir size. Methods. Thirty treated subjects with CD4+ T cell counts of <350 cells/mm3 despite viral suppression for ≥1 year were randomized to add raltegravir (400 mg twice daily) or matching placebo for 24 weeks. The primary end points were the proportion of subjects with undetectable plasma viremia (determined using an ultrasensitive assay with a lower limit of detection of <.3 copy/mL) and a change in the percentage of CD38+HLA-DR+CD8+ T cells in peripheral blood mononuclear cells (PBMCs). Results. The proportion of subjects with undetectable plasma viremia did not differ between the 2 groups (P = .42). Raltegravir intensification did not have a significant effect on immune activation or HIV-specific responses in PBMCs or gut-associated lymphoid tissue. Conclusions. Low-level viremia is not likely to be a significant cause of suboptimal CD4 + T cell gains during HIV treatment. Clinical Trials Registration. NCT00631449.

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