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Intensification of a raltegravir-based regimen with maraviroc in early HIV-1 infection

Puertas, Maria C.a,*; Massanella, Martaa,*; Llibre, Josep M.b,*; Ballestero, Monicaa; Buzon, Maria J.a; Ouchi, Dana; Esteve, Annac; Boix, Jaumed; Manzardo, Christiane; Miró, Josep M.e; Gatell, Josep M.e; Clotet, Bonaventuraa,b; Blanco, Juliàa; Martinez-Picado, Javiera,fthe MaraviBoost Collaborative Group

doi: 10.1097/QAD.0000000000000066
Clinical Science

Background: Latent HIV-1-infected cells generated early in the infection are responsible for viral persistence, and we hypothesized that addition of maraviroc to triple therapy in patients recently infected with HIV-1 could accelerate decay of the viral reservoir.

Methods: Patients recently infected (<24 weeks) by chemokine receptor 5 (CCR5)-using HIV-1 were randomized to a raltegravir + tenofovir/emtricitabine regimen (control arm, n = 15) or the same regimen intensified with maraviroc (+MVC arm, n = 15). Plasma viral load, cell-associated HIV-1 DNA (total, integrated, and episomal), and activation/inflammation markers were measured longitudinally.

Results: Plasma viral load decayed in both groups, reaching similar residual levels at week 48. Total cell-associated HIV-1 DNA also decreased in both groups during the first month, although subsequently at a slightly faster rate in the +MVC arm. The transient increase in two long terminal repeat (2-LTR) circles observed in both groups early after initiation of treatment decreased earlier in MVC-treated individuals. Early (week 12) increase of CD4+ T-cell counts was higher in the +MVC arm. Conversely, CD8+ T-cell counts and CD4+ T-cell activation decreased slower in the +MVC arm. Absolute CD4+ T-cell and CD8+ T-cell counts, immune activation, CD4+/CD8+ T-cell ratio, and soluble inflammation markers were similar in both arms at the end of the study.

Conclusion: Addition of maraviroc in early integrase inhibitor-based treatment of HIV-1 infection results in faster reduction of 2-LTR+ newly infected cells and recovery of CD4+ T-cell counts, and a modest reduction in total reservoir size after 48 weeks of treatment. Paradoxically, CCR5 blockade also induced a slower decrease in plasma viremia and immune activation.

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aAIDS Research Institute IrsiCaixa, Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona

b‘Lluita contra la SIDA’ Foundation, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona

cCenter for Epidemiological Studies on STI and HIV/AIDS of Catalonia

dHospital Universitari Germans Trias i Pujol, Badalona

eHospital Clinic – IDIBAPS, University of Barcelona

fCatalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain.

*Maria C. Puertas, Marta Massanella, and Josep M. Llibre have contributed equally to the writing of this article.

Correspondence to Julià Blanco, AIDS Research Institute IrsiCaixa, Hospital GermansTrias i Pujol, Ctra. del Canyet s/n, 08916, Badalona, Barcelona, Spain. Tel: +34 934656374; e-mail: jblanco@irsicaixa.es

Received 9 August, 2013

Revised 3 September, 2013

Accepted 5 September, 2013

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com).

© 2014 Lippincott Williams & Wilkins, Inc.