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


doi: 10.1097/QAD.0000000000000066



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.


Read abstract online in AIDS

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

Grupos de IrsiCaixa vinculados: HIVACATRetrovirología y Estudios Clínicos (GREC)Virología e Inmunología Celular (VIC)