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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.
Antivir Ther. 2012; 17(7):1301-9.AT

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.

Authors+Show Affiliations

Division of Infectious Diseases, Department of Medicine, National Jewish Health, Denver, CO, USA. lichtensteink@njhealth.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22948290

Citation

Lichtenstein, Kenneth A., et al. "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." Antiviral Therapy, vol. 17, no. 7, 2012, pp. 1301-9.
Lichtenstein KA, Armon C, Nagabhushanam V, et al. 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. Antivir Ther. 2012;17(7):1301-9.
Lichtenstein, K. A., Armon, C., Nagabhushanam, V., Efaw, B. J., Frazer-Abel, A., Hiserote, M. E., & Alam, R. (2012). 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. Antiviral Therapy, 17(7), 1301-9. https://doi.org/10.3851/IMP2350
Lichtenstein KA, et al. 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. Antivir Ther. 2012;17(7):1301-9. PubMed PMID: 22948290.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Lichtenstein,Kenneth A, AU - Armon,Carl, AU - Nagabhushanam,Vijaya, AU - Efaw,Benjamin J, AU - Frazer-Abel,Ashley, AU - Hiserote,Melissa E, AU - Alam,Rafeul, Y1 - 2012/09/05/ PY - 2012/03/05/accepted PY - 2012/9/6/entrez PY - 2012/9/6/pubmed PY - 2013/4/27/medline SP - 1301 EP - 9 JF - Antiviral therapy JO - Antivir Ther VL - 17 IS - 7 N2 - 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. SN - 2040-2058 UR - https://www.unboundmedicine.com/medline/citation/22948290/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_ L2 - http://www.diseaseinfosearch.org/result/9735 DB - PRIME DP - Unbound Medicine ER -