Marco Ripa1, Manuela Pogliaghi2, Stefania Chiappetta2, Silvia Nozza2, Alessandro Soria3, Giacomo Coppalini4, Cristina Rovelli4, Giuseppe Tambussi2. 1. IRCCS Ospedale San Raffaele, Department of Infectious and Tropical Diseases, Milan, Italy. Electronic address: ripa.marco@hsr.it. 2. IRCCS Ospedale San Raffaele, Department of Infectious and Tropical Diseases, Milan, Italy. 3. Ospedale San Gerardo, Division of Infectious Diseases, Monza, Italy. 4. Università Vita-Salute San Raffaele, Milan, Italy.
Abstract
BACKGROUND: Multi-targeted treatment strategies including maraviroc (MVC) during Primary HIV Infection (PHI) may benefit from the immune-modulatory properties of this CCR5-inhibitor. OBJECTIVES: We conducted a proof-of-concept clinical trial aimed at assessing whether maraviroc in addition of a combination antiretroviral therapy (cART) initiated during PHI would improve immunological and virological parameters. STUDY DESIGN: The MAIN (Maraviroc in HIV Acute INfection) study was a randomized open-label clinical trial (EUDRACT number: 2008-007004-29) which enrolled 29 patients with PHI. Subjects were randomly assigned to receive cART-only (cART), cART+8 weeks of MVC (ST-MVC) or cART+48 weeks of MVC (LT-MVC), regardless of predicted co-receptor usage. After 48 weeks patients in ST-MVC and LT-MVC groups discontinued MVC. Patients were evaluated at week 48 and at week 96 of follow-up to assess differences in CD4 T-cell gain and plasma HIV-RNA. RESULTS:Twenty-nine patients were enrolled. Seven patients (24%) had a predicted CXCR4 co-receptor usage. At week 48, 27 patients (93.1%) reached HIV-RNA<50cps/mL. Median CD4 T-cell count increase was 313 cells/μL (p<0.001, Wilcoxon signed-rank test). At multivariate linear regression analysis, LT-MVC arm had the greatest CD4 T-cell increase, while patients in ST-MVC arm had the least gain in CD4 T-cells (p=0.007). At week 96, multivariate analysis showed no associations between former treatment arm and CD4 T-cell gain. CONCLUSIONS: The MAIN study showed that MVC for 48 weeks in addition to cART during PHI was able to enhance CD4 T-cell gain, regardless of co-receptor usage. After MVC discontinuation, the difference between treatment arms was lost. Copyright Â
RCT Entities:
BACKGROUND: Multi-targeted treatment strategies including maraviroc (MVC) during Primary HIV Infection (PHI) may benefit from the immune-modulatory properties of this CCR5-inhibitor. OBJECTIVES: We conducted a proof-of-concept clinical trial aimed at assessing whether maraviroc in addition of a combination antiretroviral therapy (cART) initiated during PHI would improve immunological and virological parameters. STUDY DESIGN: The MAIN (Maraviroc in HIV Acute INfection) study was a randomized open-label clinical trial (EUDRACT number: 2008-007004-29) which enrolled 29 patients with PHI. Subjects were randomly assigned to receive cART-only (cART), cART+8 weeks of MVC (ST-MVC) or cART+48 weeks of MVC (LT-MVC), regardless of predicted co-receptor usage. After 48 weeks patients in ST-MVC and LT-MVC groups discontinued MVC. Patients were evaluated at week 48 and at week 96 of follow-up to assess differences in CD4 T-cell gain and plasma HIV-RNA. RESULTS: Twenty-nine patients were enrolled. Seven patients (24%) had a predicted CXCR4 co-receptor usage. At week 48, 27 patients (93.1%) reached HIV-RNA<50cps/mL. Median CD4 T-cell count increase was 313 cells/μL (p<0.001, Wilcoxon signed-rank test). At multivariate linear regression analysis, LT-MVC arm had the greatest CD4 T-cell increase, while patients in ST-MVC arm had the least gain in CD4 T-cells (p=0.007). At week 96, multivariate analysis showed no associations between former treatment arm and CD4 T-cell gain. CONCLUSIONS: The MAIN study showed that MVC for 48 weeks in addition to cART during PHI was able to enhance CD4 T-cell gain, regardless of co-receptor usage. After MVC discontinuation, the difference between treatment arms was lost. Copyright Â