Two-year safety and virologic efficacy of maraviroc in treatment-experienced patients with CCR5-tropic HIV-1 infection: 96-week combined analysis of MOTIVATE 1 and 2

Abstract

Background: Maraviroc, the first approved CCR5 antagonist, demonstrated 48-week safety and virologic efficacy in CCR5-tropic HIV-infected, treatment-experienced patients; however, critical longer-term safety and durability of responses are unknown.

Methods: Two-year follow-up of 2 prospective, randomized, blinded studies of maraviroc once daily or twice daily, or placebo in treatment-experienced patients with R5-tropic HIV-1 receiving an optimized background regimen. Unblinding occurred after the week-48 visit of the last enrolled patient. Safety and virologic parameters were assessed through week 96.

Results: One thousand forty-nine patients were randomized and received study drugs. HIV-1 RNA was <50 copies per milliliter at week 96 in 39% and 41% of patients receiving maraviroc every day or twice a day, respectively. Among patients with HIV-1 RNA <50 copies per milliliter at week 48, 81% and 87% of patients receiving maraviroc every day or twice a day, respectively, maintained this response at week 96. At week 96, median CD4+ T-cell counts increased from baseline by 89 and 113 cells per cubic millimeter with maraviroc every day and twice a day, respectively. Exposure-adjusted rates of adverse events were similar with maraviroc or placebo. No new or unexpected events were observed after week 48.

Conclusions: Maraviroc-containing antiretroviral regimens maintained durable responses in treatment-experienced patients with R5 HIV-1 through 96 weeks of treatment with a safety profile similar to placebo.

Trial registration: ClinicalTrials.gov NCT00098306 NCT00098722.

Figures

FIGURE 1

A, Study design, and B, duration of blinded study treatment. A, Patients were stratified by enfuvirtide use and HIV-1 RNA 100,000 copies per milliliter. Patients without treatment failure at end of blinded therapy (last patient week-48 visit) were given the option to roll over to open-label MVC twice a day. Week 96 efficacy analysis included all patients Post week 48. Safety analysis included only patients on blinded randomized therapy between individual week 48 visit and end of blinded therapy. B, Median (bars) and range (lines) of study treatment duration at indicated study time point.

FIGURE 2

A, Percentage of patients with HIV-1 RNA 3 times the baseline HIV-1 RNA level. Does not include patients who discontinued for lack of efficacy reasons: adverse events (n = 4); withdrew/lost to follow-up (n = 8); other reasons (n = 4); no discontinuation and no data at 96 weeks (n = 4).

FIGURE 3

Adverse events occurring in ≥5% of patients at end of blinded therapy. Includes all patients who received at least 1 dose of study medication. If the same patient in a given treatment had more than 1 occurrence in the same preferred term event category, only the most severe occurrence is taken. Event counts are adjusted to 100 years of patient exposure. Includes data up to 7 days after last dose of study drug. RTI, respiratory tract infection.

FIGURE 4

Incidence of A, total malignancies at week 48 and at end of blinded therapy, and B, exposure-adjusted malignancies by type at end of blinded therapy. *Includes anal cancer stage 0; **T-cell, B-cell and diffuse large B-cell lymphoma; †Includes testicular and tongue neoplasms; §Includes bone, liver and peritoneum; ‡Includes squamous cell carcinoma of the skin.