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Original article

A pilot study to assess inflammatory biomarker changes when raltegravir is added to a virologically suppressive HAART regimen in HIV-1-infected patients with limited immunological responses

Kenneth A Lichtenstein, Carl Armon, Vijaya Nagabhushanam, Benjamin J Efaw, Ashley Frazer-Abel, Melissa E Hiserote, Rafeul Alam

Corresponding author name: Kenneth A Lichtenstein
Corresponding author e-mail: lichtensteink@njhealth.org

Citation: Antiviral Therapy 2012; 17:1301-1309
doi: 10.3851/IMP2350

Date accepted: 05 March 2012
Date published online: 05 September 2012

Abstract

Background: Despite successful suppression of HIV-1 with HAART, some patients do not have robust immunological recovery. Chronic inflammation from persistent immune activation could contribute to this poor response, resulting in HIV-1 disease progression and the development of some non-HIV-1 comorbidities.

Methods: We conducted a pilot study of 30 HIV-1-infected patients with undetectable viral loads and poor CD4+ T-cell responses on long-term stable HAART to assess whether the addition of raltegravir would have an effect on biomarkers of chronic inflammation. A total of 26 patients were followed for 1 year on the intensified regimen. In addition to T-cell responses, we evaluated changes in activated CD4+ and CD8+ T-cells, several pro-inflammatory cytokines and chemokines and memory cell responses to HIV-1-associated peptides.

Results: Although there was no improvement in CD4+ T-cell counts, the percentage change in CD4+%, CD4+/CD8+ ratios and RANTES (regulated on activation normal T-cells expressed and secreted) increased significantly while the percentage change in CD8+ T-cell counts and CD8+%, activated CD4+ T-cells and several pro-inflammatory chemokines and cytokines decreased significantly. The percentage change in HIV-1-specific nef, pol set 1, gag and env memory T-cells also declined.

Conclusions: The addition of raltegravir to a virologically suppressive HAART regimen in patients with poor immunological responses resulted in the reduction of several pro-inflammatory biomarkers; increases were seen in RANTES levels and CD4+/CD8+ T-cell ratios. The clinical relevance of these observations is beyond the scope of this study.

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