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 - 2012/9/24
Y1 - 2012/9/24
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.
AB - 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.
KW - bacterial translocation
KW - gut-homing markers
KW - HIV reservoir
KW - immune activation
KW - residual replication
KW - treatment intensification
UR - http://www.scopus.com/inward/record.url?scp=84866707088&partnerID=8YFLogxK
U2 - 10.1097/QAD.0b013e3283584521
DO - 10.1097/QAD.0b013e3283584521
M3 - Article
C2 - 22992577
AN - SCOPUS:84866707088
SN - 0269-9370
VL - 26
SP - 1885
EP - 1894
JO - Aids
JF - Aids
IS - 15
ER -