Maraviroc in addition to cART during primary HIV infection: Results from MAIN randomized clinical trial and 96-weeks follow-up

J Clin Virol. 2016 Dec:85:86-89. doi: 10.1016/j.jcv.2016.10.016. Epub 2016 Oct 31.

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.

Keywords: CD4; HIV; Maraviroc; Primary HIV infection.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Anti-Retroviral Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active / methods*
  • CCR5 Receptor Antagonists / therapeutic use*
  • CD4 Lymphocyte Count
  • Cocaine- and Amphetamine-Regulated Transcript Protein
  • Cyclohexanes / therapeutic use*
  • Female
  • Follow-Up Studies
  • HIV Infections / drug therapy*
  • Humans
  • Male
  • Maraviroc
  • Middle Aged
  • Nerve Tissue Proteins
  • RNA, Viral / blood
  • Treatment Outcome
  • Triazoles / therapeutic use*
  • Viral Load

Substances

  • Anti-Retroviral Agents
  • CCR5 Receptor Antagonists
  • Cyclohexanes
  • Nerve Tissue Proteins
  • RNA, Viral
  • Triazoles
  • Cocaine- and Amphetamine-Regulated Transcript Protein
  • Maraviroc