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The effect of intensification with raltegravir on the HIV-1 reservoir of latently infected memory CD4 T cells in suppressed patients.
AIDS. 2012 Sep 24; 26(15):1885-94.AIDS

Abstract

OBJECTIVES

The stability of the reservoir of latently infected memory CD4 T-cells may be associated with continuous replenishment from residual HIV-1, not completely eliminated by otherwise successful antiretroviral therapy (ART). Treatment intensification could help to control residual virus and to modify the latent reservoir. The objective of this work is to assess the effect of intensifying therapy with raltegravir on the HIV-1 cell reservoir.

DESIGN

A pilot open-label phase-II clinical trial was performed to analyze ART intensification with raltegravir after 48 weeks in chronically HIV-1-infected patients on stable ART.

METHODS

We measured the number of latently infected memory CD4 T cells, residual viremia, 2-long terminal repeat circles, CD4/CD8 T-cell activation, lymphocyte subpopulations, gut homing receptor, and bacterial translocation.

RESULTS

A significant decay of HIV-1 latent reservoir was observed after intensification in the nine patients included (P = 0.021). No variation was found in either residual viremia or 2-long terminal repeat circles, whereas CD8 T-cell activation decreased at week 36 (P = 0.028). No differences were found in naive T-cell or effector memory cell counts, and the frequencies of gut homing receptor on activated or effector memory CD8 T cells. Bacterial translocation was stable, with the exception of a late decrease in lipopolysaccharide levels.

CONCLUSIONS

In this pilot noncomparative trial, treatment intensification with raltegravir significantly decreased the latent cellular HIV-1 reservoir and CD8 T-cell activation. Despite the limitations inherent to trial design, our results suggest that ART intensification should be considered as an adjuvant strategy to eradicate HIV-1 infection.

Authors+Show Affiliations

Department of Infectious Diseases, Hospital Universitario Ramón y Cajal and IRYCIS, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22992577

Citation

Vallejo, Alejandro, et al. "The Effect of Intensification With Raltegravir On the HIV-1 Reservoir of Latently Infected Memory CD4 T Cells in Suppressed Patients." AIDS (London, England), vol. 26, no. 15, 2012, pp. 1885-94.
Vallejo A, Gutierrez C, Hernandez-Novoa B, et al. The effect of intensification with raltegravir on the HIV-1 reservoir of latently infected memory CD4 T cells in suppressed patients. AIDS. 2012;26(15):1885-94.
Vallejo, A., Gutierrez, C., Hernandez-Novoa, B., Diaz, L., Madrid, N., Abad-Fernandez, M., Dronda, F., Perez-Elias, M. J., Zamora, J., Muñoz, E., Muñoz-Fernandez, M. A., & Moreno, S. (2012). The effect of intensification with raltegravir on the HIV-1 reservoir of latently infected memory CD4 T cells in suppressed patients. AIDS (London, England), 26(15), 1885-94.
Vallejo A, et al. The Effect of Intensification With Raltegravir On the HIV-1 Reservoir of Latently Infected Memory CD4 T Cells in Suppressed Patients. AIDS. 2012 Sep 24;26(15):1885-94. PubMed PMID: 22992577.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of intensification with raltegravir on the HIV-1 reservoir of latently infected memory CD4 T cells in suppressed patients. AU - Vallejo,Alejandro, AU - Gutierrez,Carolina, AU - Hernandez-Novoa,Beatriz, AU - Diaz,Laura, AU - Madrid,Nadia, AU - Abad-Fernandez,María, AU - Dronda,Fernando, AU - Perez-Elias,María J, AU - Zamora,Javier, AU - Muñoz,Eduardo, AU - Muñoz-Fernandez,María A, AU - Moreno,Santiago, PY - 2012/9/21/entrez PY - 2012/9/21/pubmed PY - 2013/3/5/medline SP - 1885 EP - 94 JF - AIDS (London, England) JO - AIDS VL - 26 IS - 15 N2 - OBJECTIVES: The stability of the reservoir of latently infected memory CD4 T-cells may be associated with continuous replenishment from residual HIV-1, not completely eliminated by otherwise successful antiretroviral therapy (ART). Treatment intensification could help to control residual virus and to modify the latent reservoir. The objective of this work is to assess the effect of intensifying therapy with raltegravir on the HIV-1 cell reservoir. DESIGN: A pilot open-label phase-II clinical trial was performed to analyze ART intensification with raltegravir after 48 weeks in chronically HIV-1-infected patients on stable ART. METHODS: We measured the number of latently infected memory CD4 T cells, residual viremia, 2-long terminal repeat circles, CD4/CD8 T-cell activation, lymphocyte subpopulations, gut homing receptor, and bacterial translocation. RESULTS: A significant decay of HIV-1 latent reservoir was observed after intensification in the nine patients included (P = 0.021). No variation was found in either residual viremia or 2-long terminal repeat circles, whereas CD8 T-cell activation decreased at week 36 (P = 0.028). No differences were found in naive T-cell or effector memory cell counts, and the frequencies of gut homing receptor on activated or effector memory CD8 T cells. Bacterial translocation was stable, with the exception of a late decrease in lipopolysaccharide levels. CONCLUSIONS: In this pilot noncomparative trial, treatment intensification with raltegravir significantly decreased the latent cellular HIV-1 reservoir and CD8 T-cell activation. Despite the limitations inherent to trial design, our results suggest that ART intensification should be considered as an adjuvant strategy to eradicate HIV-1 infection. SN - 1473-5571 UR - https://www.unboundmedicine.com/medline/citation/22992577/The_effect_of_intensification_with_raltegravir_on_the_HIV_1_reservoir_of_latently_infected_memory_CD4_T_cells_in_suppressed_patients_ L2 - https://doi.org/10.1097/QAD.0b013e3283584521 DB - PRIME DP - Unbound Medicine ER -