@article{116bb1eba24f4885b259eb2b5f062c5d,
title = "HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects",
abstract = "Highly active antiretroviral therapy (HAART) results in potent and durable suppression of HIV-1 viremia. However, HIV-1 replication resumes if therapy is interrupted. Although it is generally believed that active replication has been halted in individuals on HAART, immune activation and inflammation continue at abnormal levels, suggesting continued, low-level viral replication. To assess whether active replication might be driving immune activation in HAART, we examined the impact of treatment intensification with the integrase inhibitor raltegravir on viral complementary DNA and immune activation parameters. In the presence of raltegravir, linear HIV-1 cDNA is prevented from integrating into chromatin and is subsequently converted to episomal cDNAs. Raltegravir intensification of a three-drug suppressive HAART regimen resulted in a specific and transient increase in episomal DNAs in a large percentage of HAART-suppressed subjects. Furthermore, in subjects with these episomal DNAs, immune activation was higher at baseline and was subsequently normalized after raltegravir intensification. These results suggest that, despite suppressive HAART, active replication persists in some infected individuals and drives immune activation. The ability of raltegravir intensification to perturb the reservoir that supports active replication has implications for therapeutic strategies aimed at achieving viral eradication.",
author = "{J Buz{\'o}n}, Maria and Marta Massanella and Llibre, {Josep M.} and Anna Esteve and Viktor Dahl and Puertas, {Maria C.} and Gatell, {Josep M.} and Pere Domingo and Roger Paredes and Mark Sharkey and Sarah Palmer and Mario Stevenson and Bonaventura Clotet and Juli Blanco and Javier Martinez-Picado",
note = "Funding Information: We are grateful to the Integral study group members R. Escrig, M. Lar{\'u}s, I. Bravo and J. Puig for clinical monitoring during the study and to R. Ay{\'e}n, T. Gonz{\'a}lez and E. Grau for sample processing. We thank N. Hosoya and D.R. Kuritzkes (Massachusetts General Hospital, Boston) for providing the plasmid to generate the standard for the integrated HIV-1 DNA quantification. We wish to thank the volunteers who participated in this study. This study was supported by the Spanish AIDS network {\textquoteleft}Red Tem{\'a}tica Cooperativa de Investigaci{\'o}n en SIDA{\textquoteright} (RD06/0006), by funding from the European Community{\textquoteright}s Seventh Framework Program (FP7/2007-2013) under the Collaborative HIV and Anti-HIV Drug Resistance Network grant agreement 223131, by funding from the US National Institutes of Health to M. Stevenson and by an unrestricted grant from Merck Sharp & Dohme. J.B. is a researcher from Fundaci{\'o} Institut de Recerca en Ci{\`e}ncies de la Salut Germans Trias i Pujol supported by the Instituto de Salud Carlos III and the Health Department of the Catalan Government (Generalitat de Catalunya). M.J.B. and M.M. were supported by Ag{\`e}ncia de Gesti{\'o} d{\textquoteright}Ajuts Universitaris i de Recerca from Generalitat de Catalunya and the European Social Fund. M.M. is appointed to the Pompeu Fabra University PhD program. S.P. was funded, in part, by the Swedish Research Council and by 107170-44-RGRL from the Foundation for AIDS Research.",
year = "2010",
month = apr,
doi = "10.1038/nm.2111",
language = "English (US)",
volume = "16",
pages = "460--465",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "4",
}