Effects of Maraviroc vs. Efavirenz on CD4/CD8 Ratio
Condition: HIV/AIDS
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Study type: Interventional
Phase: Phase 3

Summary: 
      A low CD4/CD8 ratio is considered a surrogate marker of immunosenescence and is an
      independent predictor of non-AIDS-related morbidity and mortality. Given the strong clinical
      implications the impact of different regimens on the CD4/CD8 ratio recovery needs to be
      analyzed. The MERIT study is a completed a randomized, double-blind, multicenter phase
      IIb/III study with an open-label extension phase (240-week follow-up) to assess the efficacy
      of zidovudine/lamivudine in combination with maraviroc (MVC) or efavirenz (EFV) in
      treatment-naïve patients. Anonymised patient level data of the MERIT trial to compare the
      trajectories of the CD4/CD8 ratio of participants treated with maraviroc vs. efavirenz will
      be used.
    

Detailed description: 
      The Merit study was a randomized, double-blind, active-comparator multicenter, phase IIb/III
      study, treatment- naive patients (aged at least 16 years) with R5 HIV-1, and with plasma
      viral load (HIV-1 RNA) above 2000 copies/ml, who received MVC 300mg q.d., MVC 300mg b.i.d.,
      or EFV 600mg q.d., each in combination with ZDV/3TC 300 mg/150mg b.i.d. Key exclusion
      criteria included prior treatment with EFV, ZDV, 3TC, or any antiretroviral for more than 14
      days at any time, and evidence of resistance to EFV, ZDV, or 3TC, as indicated by the
      presence of at least one nucleoside-associated mutations conferring resistance to ZDV, or
      phenotypic resistance to ZDV, at least one mutation conferring resistance to 3TC or
      phenotypic resistance to 3TC, or at least one mutation responsible for EFV resistance or
      phenotypic resistance to EFV.

      Following a planned analysis at week 16, the MVC q.d. arm was discontinued for not meeting
      prespecified efficacy criteria, and the study continued with two treatment arms. The sponsor
      was unblinded at the 48-week analysis time point, but the investigators and patients remained
      blinded until the 96-week analysis. The study was then fully unblinded following the last
      patient's 96-week visit, and patients were enrolled in a nominal 3-year open-label phase.
      Efficacy and safety data from the 240-week (nominal 5-year) study duration have been recently
      published (Cooper D. et al, AIDS 2014).

      The longitudinal data of the Merit study (240-week follow-up) will be analysed. The current
      long-term follow-up of the MERIT study, the extensive registry of both AIDS and non-AIDS
      clinical events and the randomization to a therapeutic intervention including maraviroc, will
      allow to evaluate the effects of maraviroc vs. efavirenz on the CD4/CD8 ratio trajectories.

      All randomized subjects included in MERIT will be included in this exploratory post hoc
      analysis. For the principal objective, longitudinal changes in CD4 and CD8 counts and in the
      CD4/CD8 ratio will be assessed using generalized estimating equations. Interaction terms will
      be created to assess whether these changes over time differed significantly between treatment
      arms. Kaplan-Meier methods will be used to calculate the rates of CD4/CD8 normalization at
      0.4 and 1 cut-offs and cumulative probabilities. Cox proportional hazard models will be used
      to compare probabilities of CD4/CD8 normalization by treatment arm.
    

Intervention name(s): Maraviroc (UK-427,857) QD + Zidovudine/Lamivudine BID; Efavirenz QD + Zidovudine/Lamivudine BID; Maraviroc (UK-427,857) BID + Zidovudine/Lamivudine QD
Intervention type(s): Drug; Drug; Drug
Intervention description(s): maraviroc (UK-427,857) 300 mg once daily added to zidovudine/lamivudine (300 mg/150 mg twice daily; efavirenz (600 mg once daily) added to zidovudine/lamivudine (300 mg/150 mg twice daily); maraviroc (UK-427,857) 300 mg twice daily added to zidovudine/lamivudine (300 mg/150 mg twice daily
Intervention MeSH terms: Lamivudine; Zidovudine; Efavirenz; Maraviroc
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: HIV; CD4/CD8 ratio; immune recovery; maraviroc; efavirenz