POSITIVELY AWARE NOVEMBER/DECEMBER 2010
CONFERENCE REPORT: ICAAC 2010
Reported by Enid Vázquez
New, improved therapies move forward
A summary of HIV research presented in September at the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), held in Boston. Visit www.icaac.org.
TMC278, Atripla, and resistance
One of the most talked-about presentations at ICAAC was the delineation of drug resistance with the experimental HIV drug TMC278 (rilpivirine). The comparison of TMC278 to Atripla in the THRIVE and ECHO studies was presented at the International AIDS Conference in July and featured in the September/October issue, “Tales from Vienna.”
In Boston, Tibotec Pharmaceuticals reported on drug resistance data from the two studies. Basically, it appeared that in participants who were less adherent with their medication, the people taking TMC278 had a greater risk of developing drug resistance and treatment failure than did the folks on Atripla. Not the best news for the awaited new drug, showing less forgiveness for missed doses, although it was balanced by greater tolerability compared to Atripla. See The Buzz on page 42 for more information.
Atripla rival gets good news
Still in the experimental stage, the Quad tablet—like Atripla—provides a complete HIV regimen in one pill taken once a day. It consists of the experimental integrase inhibitor drug elvitegravir along with an experimental booster medication called cobicistat (see below), plus the popular Truvada (itself a combination drug made up of Viread and Emtriva).
Earlier this year, researchers reported that the Quad was non-inferior to the bestselling Atripla in early 24-week data. Now, 48-week data shows that the Quad continues to be non-inferior to Atripla.
In virologic suppression (viral load of less than 50 copies per mL), the Quad tablet was 90% successful compared to 83% for Atripla. These results were in a Phase 2 study with small numbers of people, however: 48 study participants taking the Quad and 23 taking Atripla. A large international Phase 3 study with 700 participants is underway.
Goodbye, Norvir—hello, cobicistat?
Comparing Reyataz boosted by Norvir to Reyataz boosted by the experimental cobicistat (see below), earlier 24-week data found non-inferiority for the two boosters. Now, at 48 weeks, cobicistat continues to show non-inferiority to Norvir. 84% of the cobicistat group vs. 86% of the Norvir group achieved a viral load of less than 50 copies per mL. As with the Quad study above, these results were from small Phase 2 research, with 50 individuals on cobicistat and 29 on Norvir. The clinical trial, in which Truvada is given as the background medication, is now in a large Phase 3 international study with 700 individuals.
Unfortunately, there was no advantage for cobicistat in lipid levels or gastrointestinal distress. There was some concern from the earlier 24-week results about potential kidney toxicity (see The Buzz, May/June), but there doesn’t seem to be a problem so far, although an initial increase in creatinine (a sign of kidney damage) is seen with cobicistat. There may, however, be a decrease in tubular secretion of creatine, which is not evidence of kidney damage.
In a study of people who started out taking Reyataz with Norvir, those who dumped the Norvir continued to do well out to 120 weeks.
Norvir helps improve blood levels of Reyataz and thus increases efficacy and limits the development of drug resistance, but it comes at the price of lipid increases and frequent tolerability problems.
The ARIES study had earlier shown the non-inferiority of unboosted Reyataz to Reyataz boosted by Norvir, out to 84 weeks. People in the study were treatment naïve (taking HIV medication for the first time, a group that generally has the best results).
Here, the vast majority (88%) of the 419 participants in ARIES continued on the study out to 144 weeks. These 369 participants, divided between the boosted and the unboosted drug regimens, experienced similar treatment efficacy. About 84% of all participants had a viral load of less than 50 copies per mL at 120 weeks. They also had the same CD4+ T-cell increase: a median of 290 (half had more than this, half had less).
All study participants were taking Epzicom (a combination of Ziagen and Epivir) as their background medication. Epzicom, however, is considered an alternative background medication under U.S. HIV treatment guidelines. The preferred background combination drug, Truvada (Viread + Emtriva), cannot be used with Reyataz because Viread lowers Reyataz levels, making Norvir necessary.
Also of note: an earlier study showed a higher rate of treatment failure with unboosted Reyataz compared to boosted Reyataz. The difference in results may be because everyone in Aries started with boosted Reyataz, and in the other study there were some who were randomized to start with unboosted Reyataz.
Out in the real world, people on boosted Reyataz shouldn’t just stop taking Norvir. An HIV specialist can walk a patient through their options.
In rare news about Viramune, an experimental once-daily formulation of the drug was found to be non-infeior to the regular twice-daily tablet currently on the market, as first reported at the International AIDS Conference in July.
In the VERxVE study, Viramune XR (extended release), a 400 mg pill taken once a day, was compared to Viramune IR (immediate release), a 200 mg tablet taken twice a day, divided between 1,011 participants. Past research had found that while the pharmacokinetics of the IR tablets support once daily dosing, there was greater intolerability when two IR tablets were taken together once a day.
“Once-daily dosing with Viramune XR provides patients with a more convenient treatment regimen with comparable efficacy and safety to Viramune IR,” the study concluded. However, the risk of side effects such as liver toxicity and Stevens-Johnson syndrome (a potentially life-threatening rash) did not decrease.
The TRANxITION study looked at switching people from Viramune to Viramune XR. The results are still early, 24 weeks, but showed non-inferiority of treatment effectiveness for the switch group. Viral load remained undetectable (less than 50 copies per mL) in 95% (295 participants) of the switch group, versus 92% (148) of the participants still taking Viramune twice a day.
Prezista drug resistance
Tibotec Therapeutics presented a subgroup analysis of drug resistance in their ODIN study, comparing once-daily to twice-daily Prezista. “Virologic failure was low and similar between arms [once daily vs. twice daily], rarely resulting in resistance,” the company reported. See presentation H-1811 at www.icaac.org for details of drug resistance changes found in the study subanalysis.
ODIN is a Phase 3 study with nearly 600 treatment-experienced participants, none of whom had drug resistance to Prezista at the start of the trial and all of whom had more than 1,000 viral load when entering the study. The once-daily dose consisted of 800 mg Prezista with 100 mg Norvir and the twice-daily dose was 600 mg Prezista with 100 mg Norvir. Participants were also given an optimized background therapy (OBT); medications that should work the best for them given the results of their HIV drug resistance testing.
An important caveat in this study is that participants from the beginning had minimal drug resistant changes in their virus to Prezista and to the entire class of medications it’s from, the HIV protease inhibitors. Therefore, it’s not surprising that the once-daily dose used in treatment-naïve people would be as effective as the twice-daily dose for highly treatment-experienced patients with drug resistant virus.
Thanks to Joel Gallant, MD, for his thoughtful review.