Switching to Isentress The SPIRAL study reported that Isentress was non-inferior to a Norvir-boosted protease inhibitor medication out to 48 weeks. About 88% of study participants had an undetectable viral load whether they stayed on their regimen or switched to Isentress. The 273 study participants were about evenly divided between switching or staying on their current treatment. The ODIS study from Spain also found that switching people from a protease inhibitor therapy to Isentress works well. At 24 weeks after switching to Isentress, 94% of 222 participants remained undetectable. Looking at the 6% of people experiencing treatment failure after the switch, the Spanish researchers found that HIV resistance to the other drugs in the regimens used (nucleoside medications) was the primary reason that treatment failed. Last year, however, a larger study (SWITCHMRK) of 700 people in which half stayed on Kaletra and half were switched to Isentress had to be stopped because there were more treatment failures in the Isentress group. STARTMRK showed that when considering a switch from a boosted protease inhibitor (like Kaletra) to Isentress, it’s important to make sure that the other drugs in the regimen are fully active. ODIS also looked at switching people to once-daily vs. twice-daily Isentress, and while both were similar, there was a tendency for the once-daily dose to perform less well. Doctors at the conference noted that while the small number of participants did not allow for a statistically significant difference between these two groups, the actual numerical difference was large.
Prezista monotherapy Confusing statistics resulted from the international MONET study comparing Prezista by itself to Prezista in combination with two other HIV drugs. Looking at the same individual, Prezista monotherapy might be either successful or unsuccessful, depending on the statistical analysis used. P os i t i velyAwa re.com
MONET looked at 256 individuals who were undetectable on therapy (HIV viral load less than 50 copies), but had never taken Prezista before. They were switched to Prezista treatment, half of them on monotherapy and half taking it with other HIV drugs. In 48-week results presented last year, Prezista monotherapy was found to be non-inferior to a Prezista combination drug regimen. In these later results from 96 weeks of study presented in Vienna, however, Prezista monotherapy was not noninferior to combination therapy. The study presenters, however, showed that when you consider the people experiencing treatment failure with monotherapy who went on to have undetectable viral load at the end of the 96 weeks, the monotherapy was then non-inferior. It’s all in the switch. In most clinical studies, having to switch someone off the medication they’ve been given constitutes a failure for that therapy, no matter what. But if a switch is allowed, then experiencing success (like undetectable viral load) by switching therapy is not considered a failure. In MONET, two viral load measurements above undetectable (above 50 copies) required a switch under study standards. In these cases, monotherapy was intensified by adding back two nucleoside analog drugs. If the viral load re-suppressed to undetectable levels by the end of the study, that was considered a failure under the stricter statistical standard, but a success by the “switch allowed” standard. Intensification with two HIV nucleoside analog drugs in the monotherapy group led to re-suppression of virus below 50 copies in 7 of 8 people (88%). Moreover, most of the people who had to switch their therapy because of increased viral load actually had very low levels of increase, between 50 and 200 copies. Co-infection with hepatitis C was found to significantly increase the risk of treatment failure, and hep C co-infection was higher in the monotherapy group (19% vs. 12% for the combination folks).
As was done in this study, Prezista must always be boosted with a mini-dose (usually 100 mg) of Norvir.
TBR-652 dual CCR5/CCR2 inhibitor Data from a Phase 2a study of oral entry inhibitor TBR-652 were presented by David Martin of Tobira, the company developing the drug. Preliminary data from this study were first presented at CROI in February 2010 (see the May/June issue of Positively Aware). TBR-652 is a dual CCR5/CCR2 inhibitor. HIV uses the CCR5 receptor to gain entry into T-cells, while CCR2 is a receptor found on certain cells and is associated with chronic inflammation. This was a small, 10-day monotherapy dose-finding study, with 54 patients randomized to receive five different doses of the drug or placebo, once daily. There was an up to 1.8 log reduction in viral load for those receiving drug in the study, with one discontinuation which was not related to any adverse event. Inflammatory markers MCP-1, hsCRP, and IL-6 were measured on day 1 and day 10, with increases seen in MCP-1 concentrations and decreases in hsCRP levels. hsCRP stands for high sensitivity C-reactive protein (CRP). CRP is a protein, the levels of which rise in response to inflammation, and MCP-1 (monocyte chemotactic protein-1) has also been implicated in inflammation. To date, no significant safety signals have been identified with CCR2 antagonists. The study authors concluded that “TBR-652 warrants further investigation as an unboosted, once-daily oral CCR5 antagonist with potentially important anti-inflammatory effects.” The Phase 2b study is expected to begin in early 2011 and will include immunologic, cardiovascular, and metabolic substudies. —Jeff Berry Thanks to Joel Gallant, MD, for his thoughtful review. N ov e m b e r / D e c e m b e r 2 01 0 |
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