Clinical trial NCT03178084: Effects of Maraviroc vs. Efavirenz on CD4/CD8 Ratio
Official title: The Effects of Maraviroc Versus Efavirenz in Combination With Zidovudine/Abacavir on the CD4/CD8 Ratio in Treatment-naïve HIV-infected Individuals
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV/AIDS
Keywords: HIV
CD4/CD8 ratio
immune recovery
maraviroc
efavirenz
Lead sponsor: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
Sponsor class: OTHER
First posted: 2017-06-06
Enrollment: 721
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: All patients analysed in the Merit trial (Cooper, JAIDS 2010)

Primary outcomes:
measure: Change From Baseline in CD4/CD8 ratio
timeFrame: From baseline to week 120
Secondary outcomes:
measure: Change From Baseline in CD8+ T cells
timeFrame: From baseline to week 120
measure: Change From Baseline in CD4/CD8 ratio
timeFrame: From baseline to week 120
Other outcomes:
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