People taking Selzentry (maraviroc) had greater viral load reductions and CD4 count increases after 48 weeks compared to those taking a placebo, according to a new report at the 11th European AIDS Conference (EACS) in Madrid. These data, from the MOTIVATE 2 trial, confirm the findings of the MOTIVATE 1 trial on Pfizer’s CCR5 entry inhibitor reported at the 47th Interscience Conference on Antimocrobial Agents and Chemotherapy (ICAAC) earlier this fall in Chicago.
The MOTIVATE 2 trial is a 48 week study in people who are heavily treatment experienced and whose virus uses only the CCR5 coreceptor (see “The Trouble with Tropism” to read more about HIV coreceptors). The study enrolled 474 participants in Europe, Australia, and North America.
All patients enrolled in MOTIVATE 2 had tried and failed drug regimens involving all three classes of oral HIV drugs and had viral loads above 5,000 while on their previous treatment regimen. They were randomized to once- or twice-daily Selzentry, or placebo, in combination with an optimized background regimen (OBR) that was made up of three to six approved HIV drugs to which the study doctor’s felt they would most likely respond.
If the OBR contained Rescriptor (delavirdine) or a protease inhibitor—other than Aptivus (tipranavir) —Selzentry was dosed at 150mg either once or twice a day to avoid drug interactions. Otherwise, the Selzentry dose was 300mg either once or twice a day.
The 48-week results from MOTIVATE 2 were reported at EACS by Gerd Fätkenheuer, MD, of the department of medicine at the University of Cologne in Köln, Germany. Upon entering the study, average viral loads among patients in the three treatment groups were between 4.84 and 4.89 logs and average CD4 counts were between 173 and 182 cells. Roughly 65 percent of the study volunteers had two or fewer active drugs in their OBR.
After 48 weeks of treatment, the proportion of people with viral loads below 400 copies was significantly greater in people taking Selzentry groups compared to those taking the placebo. In those taking Selzentry once daily, 53 percent maintained less than 400 copies of virus for 48 weeks, and 55 percent of those taking it twice daily did the same. In the placebo group, only 23 percent had viral loads below 400. The difference between the Selzentry groups and placebo group were statistically significant, meaning that it wasn’t due to chance.
Viral loads below 50—undetectable using standard ultrasensitive tests—were documented in approximately 45 percent of those in both Selzentry groups, compared 18 percent in the placebo group after 48 weeks. Here, too, the differences between the Selzentry groups and the placebo group were statistically significant.
CD4 counts increased by 69 cells in the placebo group, compared with average CD4 gains of 121 cells in the once-daily Selzentry group and 128 cells in the twice-daily group.
Researchers also analyzed the difference it made if people added Fuzeon (enfuvirtide) to their OBR, and whether it was the first time they’d used the drug or if they’d already been on it for some time. For Fuzeon first-timers, roughly 62 percent of both of the dosing groups taking Selzentry had virus levels of less than 50 copies after 48 weeks, compared to 27 percent of those on placebo. For people who’d already taken Fuzeon before starting the trial, 25 percent of those taking Selzentry once daily and 32 percent taking it twice a day had less than 50 copies at 48 weeks, compared to just 3 percent of people taking the placebo.
The incidence of side effects was no greater among those in the Selzentry groups compared with those in the placebo group. The most common side effects in all three groups included diarrhea, nausea, headache and fatigue. People taking Selzentry had slightly more respiratory side effects than people taking placebo. Lastly, very few people in any group had dangerous elevations in liver enzymes, which suggests that Selzentry is a liver-friendly drug.
As reported in MOTIVATE 1, people who had virologic failure while taking Selzentry were watched closely to see if the tropism of their virus switched from CCR5 to CXCR4. People who had this switch after failing, however, still maintained CD4 counts that were significantly higher than those taking a placebo, indicating that there were no harmful effects to the immune system—as had once been feared—if a tropism switch occurs while on treatment.
Source:
Fätkenheuer G, Konourina I, Nelson M, et al. Efficacy and Safety of Maraviroc (MVC) Plus Optimized Background Therapy (OBT) in Varaemic, Antiretroviral Treatment-Experienced Patients Infected with CCR5-Tropic (R5) HIV-1 in Europe, Australia and North America (MOTIVATE 2): 48-Week Results [Abstract PS3/5]. 11th European AIDS Conference/EACS, Madrid, 2007.
