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Effect of raltegravir-containing intensification on HIV burden and T-cell activation in multiple gut sites of HIV-positive adults on suppressive antiretroviral therapy


Yukl, S A; Shergill, A K; McQuaid, K; Gianella, S; Lampiris, H; Hare, C B; Pandori, M; Sinclair, E; Günthard, H F; Fischer, M; Wong, J K; Havlir, D V (2010). Effect of raltegravir-containing intensification on HIV burden and T-cell activation in multiple gut sites of HIV-positive adults on suppressive antiretroviral therapy. AIDS, 24(16):2451-2460.

Abstract

OBJECTIVE: To determine whether raltegravir-containing antiretroviral therapy (ART) intensification reduces HIV levels in the gut.

DESIGN: Open-label study in HIV-positive adults on ART with plasma HIV RNA below 40 copies/ml.

METHODS: Seven HIV-positive adults received 12 weeks of ART intensification with raltegravir alone or in combination with efavirenz or darunavir. Gut cells were obtained by upper and lower endoscopy with biopsies from duodenum, ileum, colon, and rectum at baseline and 12 weeks. Study outcomes included plasma HIV RNA, HIV DNA and RNA from peripheral blood mononuclear cells (PBMC) and four gut sites, T-cell subsets, and activation markers.

RESULTS: Intensification produced no consistent decrease in HIV RNA in the plasma, PBMC, duodenum, colon, or rectum. However, five of seven participants had a decrease in unspliced HIV RNA per 10 CD4(+) T cells in the ileum. There was a trend towards decreased T-cell activation in all sites, which was greatest for CD8(+) T cells in the ileum and PBMC, and a trend towards increased CD4(+) T cells in the ileum.

CONCLUSION: Most HIV RNA and DNA in the blood and gut is not the result of ongoing replication that can be impacted by short-term intensification with raltegravir. However, the ileum may support ongoing productive infection in some patients on ART, even if the contribution to plasma RNA is not discernible.

OBJECTIVE: To determine whether raltegravir-containing antiretroviral therapy (ART) intensification reduces HIV levels in the gut.

DESIGN: Open-label study in HIV-positive adults on ART with plasma HIV RNA below 40 copies/ml.

METHODS: Seven HIV-positive adults received 12 weeks of ART intensification with raltegravir alone or in combination with efavirenz or darunavir. Gut cells were obtained by upper and lower endoscopy with biopsies from duodenum, ileum, colon, and rectum at baseline and 12 weeks. Study outcomes included plasma HIV RNA, HIV DNA and RNA from peripheral blood mononuclear cells (PBMC) and four gut sites, T-cell subsets, and activation markers.

RESULTS: Intensification produced no consistent decrease in HIV RNA in the plasma, PBMC, duodenum, colon, or rectum. However, five of seven participants had a decrease in unspliced HIV RNA per 10 CD4(+) T cells in the ileum. There was a trend towards decreased T-cell activation in all sites, which was greatest for CD8(+) T cells in the ileum and PBMC, and a trend towards increased CD4(+) T cells in the ileum.

CONCLUSION: Most HIV RNA and DNA in the blood and gut is not the result of ongoing replication that can be impacted by short-term intensification with raltegravir. However, the ileum may support ongoing productive infection in some patients on ART, even if the contribution to plasma RNA is not discernible.

Citations

130 citations in Web of Science®
137 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2010
Deposited On:16 Jan 2011 18:06
Last Modified:05 Apr 2016 14:29
Publisher:Lippincott Wiliams & Wilkins
ISSN:0269-9370
Publisher DOI:https://doi.org/10.1097/QAD.0b013e32833ef7bb
PubMed ID:20827162

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