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Comparative Trial of Maraviroc vs. Tenofovir/FTC Halted

News in Context |
October 17, 2013

Comparative Trial of Maraviroc vs. Tenofovir/FTC Halted

  1. Paul E. Sax, MD

Patients in the maraviroc arm had a suboptimal virologic response rate and were nearly three times as likely as those in the tenofovir/FTC arm to experience treatment failure.

  1. Paul E. Sax, MD

On October 8, 2013, ViiV Healthcare announced (in a pdf provided by the company's regional medical scientists) that a clinical trial comparing maraviroc to tenofovir/FTC was being halted by the study's data-monitoring committee.

The trial, called MODERN (standing for “Maraviroc Once-Daily with Darunavir Enhanced by Ritonavir in a Novel Regimen”), enrolled treatment-naive patients with CCR5-tropic virus. Participants were randomized to maraviroc 150 mg or tenofovir/FTC, both once daily with matching placebos, in addition to once-daily ritonavir-boosted darunavir. In a preliminary analysis of data from 791 patients, 72% of those in the maraviroc arm and 83% of those in the tenofovir/FTC arm had viral loads <50 copies/mL at week 48 (difference, –11%; 95% confidence interval, –17.1% to –6.1%; the prespecified criteria for noninferiority required that the lower bound of the 95% CI be greater than –10%). Thirty-eight patients in the maraviroc arm and 13 in the TDF/FTC arm experienced treatment failure. No new safety issues were identified in either treatment arm. Data are still being analyzed, with further information to come.

Comment

This is the latest of several clinical studies of two-drug, nucleoside reverse transcriptase inhibitor–sparing initial treatments that have come up short due to efficacy or tolerability concerns or both. Ongoing trials of note include the fully powered NEAT study comparing raltegravir to tenofovir/FTC (both with ritonavir-boosted darunavir), and the GARDEL study comparing 3TC to NRTI/3TC (both with lopinavir/ritonavir). Pending the results of these trials, clinicians should avoid using two-drug, NRTI-sparing first-line regimens except in rare circumstances — and even then, consider including 3TC or FTC.

  • Disclosures for Paul E. Sax, MD at time of publication Consultant / Advisory board Bristol-Myers Squibb; Gilead; GlaxoSmithKline; Janssen; Merck Grant / research support NIH; Bristol-Myers Squibb; Gilead; GlaxoSmithKline; Merck Editorial boards Medscape; UpToDate Leadership positions in professional societies Mass ID Society (Vice President)

Reader Comments (1)

Jose A. Giron MD Physician, Infectious Disease

Three trials using 2 drug regimens come to the same conclusion.

If HIV replicates at 10^10 particles per day and the mutation rate is assumed at at between 10^4 and 10^5, one may expect mutants to be selected out at a likely rate of 10 to 100 per day. Even at a rate of selection of 1 mutant per day, eventually that single mutant will have a selective advantage. If one then adds the potential nonadherence , a problem that is intrinsic to any long term regimen and the potential for reduced tissue penetration in certain tissues, it is clear that one needs either incredibly potent drugs to overcome the genetic barrier or at least 3 potent drugs to provide the HIV infected patient with a sufficient margin of drug efficacy.

The key issue, in my estimation , is still the goal of achieving clearance of the virus from the "sanctuary sites" and the latently infected reservoirs

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