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.
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.
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.
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: firstname.lastname@example.org
Received 9 August, 2013
Revised 3 September, 2013
Accepted 5 September, 2013
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