Novel HIV Drug a 'Trade-Off'

Este artículo, salió publicado en http://www.medpagetoday.com/MeetingCoverage/ICAAC/22219?shield=0;  y habla de una nueva droga , pero también nos menciona que debemos ser cautos en su lectura e intrerpretación, hasta que sea publicado el artículo.  Espero que les sea útil. Dr. Carlos Erazo Action Points   Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal. Clinicians should note that when TMC278 was compared with efavirenz in naive patients, both taken with two nucleoside reverse transciptase agents, overall results were similar but adherence was especially critical to TMC278's efficacy in those with baseline HIV RNA over 100,000. Clinicians should note that TMC278 appeared to be better tolerated than efavirenz in these head-to-head studies. Note that mutational patterns developing on treatment were different in the two study groups. BOSTON -- In HIV patients starting therapy, an investigational non-nucleoside reverse transcriptase inhibitor had a higher rate of virologic failure than a standard medication, researchers said here. But treatment with TMC278 (rilpivirine) also caused fewer adverse events and led to fewer dropouts for such events than efavirenz (Sustiva), according to Joseph Eron, MD, of the University of North Carolina Chapel Hill. In both arms of two nearly identical phase III trials, virologic failure was more common in those with a higher baseline viral load and suboptimal adherence, Eron said during an oral presentation here at the Interscience Conference on Antimicrobial Agents and Chemotherapy. But the effect was more apparent among those taking the novel drug, he said. In the two trials -- dubbed THRIVE and ECHO -- a total of 1,368 treatment-naive patients were randomly assigned to get either TMC278 or efavirenz, combined with two other anti-HIV medications. In the ECHO trial, all patients also got the combination of tenofovir and emtricitabine (Truvada), but in THRIVE, physicians could choose any two nucleoside reverse transcriptase inhibitors. The main goal of the study was to see if the TMC278 regimens were noninferior to the efavirenz regimens, and researchers reported at the International AIDS Conference in Vienna that that was the case. (See IAC: New HIV Drug Matches Old Standard) At the AIDS meeting, Tibotec -- the developer of the drug and the sponsor of the two trials -- announced it was filing for approval of the drug. Here, Eron was filling in some of the gaps, including how and why some patients failed to respond to the drugs. In a pooled analysis of data from the two trials, the researchers found that 84.3% of TMC278 patients had a viral load of fewer than 50 copies of HIV RNA per milliliter of serum after 48 weeks of therapy, compared with 82.3% of efavirenz patients. The result met criteria for noninferiority, he said. When the patients were analyzed on the basis of baseline viral load, the two drugs were also noninferior among those starting with more than 100,000 copies, but TMC278 was actually better among those with a viral load below that cutoff with 90% responding, compared with 84%. The proportion of patients who suffered a grade 2,3, or 4 adverse event regarded as possibly related to treatment was 16% among TMC278 patients and 31% among efavirenz patients (P<0.0001), Eron said. Moreover, only 3% of TMC278 patients dropped out because of adverse events, compared with 8% of those taking efavirenz (P=0.0005). Neurological adverse events were also significantly more common (P<0.0001) among those taking efavirenz. The incidence of virologic failure -- defined as never having suppressed HIV or having rebounded after initial success -- was 10% among TMC278 patients and 6% among those taking efavirenz. Much of the difference was driven by patients with initial viral loads greater than 100,000 copies whose adherence to therapy was poor, Eron said. Among TMC278 patients, he said, there were 42 who met both criteria and 26 of them failed therapy. Among efavirenz patients, 38 met the criteria, but only 12 failed. Among those who failed therapy, Eron reported, 63% of TMC278 patients had developed at least one mutation that was associated with resistance to non-nucleoside reverse transcriptase inhibitors, compared with 54% of efavirenz patients. Each drug had a distinct pattern of resistance-associated mutations, he said, with only one seen in both groups. "The most important new information was that patients with both a high viral load at baseline and suboptimal adherence had a higher risk of failure on TMC278 than on efavirenz," said Paul Sax, MD, of Brigham and Women's Hospital in Boston, who co-moderated the session but was not involved in the research. On the other hand, he told MedPage Today, for patients who are easier to treat -- those with a low viral load when they start therapy -- "it did better." From the clinical point of view, he said, "it's a trade-off." His co-moderator, Jens Lundgren, MD, of the University of Copenhagen, commented that it's not surprising to see fewer TMC278 patients dropping out because of adverse effects, since efavirenz is known to have central nervous system impacts that many patients find difficult to tolerate "and TMC278 doesn't have that." But the bottom line, he said, may be that TMC278 is slightly less potent, but easier to take. The study was supported by Tibotec, which is developing the drug. Eron has disclosed financial relationships with GlaxoSmithKline, Bristol-Myers Squibb, Virologic, Boehringer Ingelheim, Virco, Abbott, and Merck. Some authors were employees of Tibotec. Sax reported financial links with a range of pharmaceutical companies. Lundgren said he had no disclosures.

Primary source: Interscience Conference on Antimicrobial Agents and Chemotherapy Source reference: Rimsky L, et al "Characterization of the resistance profile of TMC278: 48-week analysis of the phase III studies ECHO and THRIVE" ICAAC 2010.

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