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

Maria C. Puertas, Marta Massanella, Josep M. Llibre, Monica Ballestero, Maria J. Buzon, Dan Ouchi, Anna Esteve, Jaume Boix, Christian Manzardo, Josep M. Miró, Josep M. Gatell, Bonaventura Clotet, Julià Blanco, Javier Martinez-Picado

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48 Citations (Scopus)

Abstract

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. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Original languageEnglish
Pages (from-to)325-334
JournalAIDS
Volume28
Issue number3
DOIs
Publication statusPublished - 28 Jan 2014

Keywords

  • Early infection
  • HIV-1
  • Maraviroc
  • Raltegravir
  • Treatment intensification
  • Viral reservoir

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