Coverage of 2007 IAS
(International AIDS Society)

July 2007, Sydney, Australia

 

Another Setback for Selzentry

July 25, 2007

A study presented during the late-breaker session at the 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention showed that the experimental CCR5 antagonist Selzentry (maraviroc) was slightly less effective than Sustiva (efavirenz) when used as part of a HAART regimen for people taking HIV drugs for the first time. This is another setback for this drug, which received an ‘approvable’ letter from the FDA in June but has yet to be fully approved by the FDA.

The MERIT study looked at over 700 people with R5-only HIV who had never taken anti-HIV drugs. People were randomly assigned to take either 300mg of Selzentry twice a day or 600mg of Sustiva once a day. Everyone in the study also took Combivir (AZT + 3TC). A once-a-day Selzentry arm was stopped early, due to poor results.

After 48 weeks of the study, similar numbers of people in both arms had stopped taking their combination, but for different reasons. Almost three times as many people taking Selzentry dropped out due to treatment failure. More people in the Sustiva group stopped due to intolerance—mostly neuropsychological side effects associated with Sustiva.

Nearly 70% of people taking Sustiva had HIV levels below 50 copies vs. 64% of people taking Selzentry. Surprisingly, this difference was only seen among people in the study from the southern hemisphere. There were several reasons hypothesized for this difference—different types (clades) of HIV or problems with the R5 screening test—but this finding remains unexplained.

Another somewhat surprising finding was that the people taking Selzentry experienced larger increases in CD4 counts- an average of 169 cells vs. 142. The difference happened mostly in the first 8 weeks of the study. This is consistent with other research on Selzentry and other R5 drugs. For example, a study presented at last year’s International AIDS Conference in Toronto found larger gains in CD4 cells among people with X4 or dual/mixed HIV who were taking Selzentry, despite no effect of HIV levels. Some have speculated that this is due to the movement of CD4 cells out of lymph nodes rather than a real increase in the number of cells. Others think this drug might have affects on the immune system independent of reducing HIV levels. More research is needed to understand this important issue.

The differences seen between Selzentry and Sustiva in this study were small, but it must still be seen as a setback. The FDA is expected to approve Selzentry for people with extensive treatment experience soon. Only about half of treatment experienced people have R5-only HIV, vs. around 4 in 5 people who have never taken HIV drugs. Many people think this makes Selzentry (and other drugs that target CCR5) a more appropriate option for people as first or second line therapy. This study does not rule out Selzentry for first line therapy, but its failure to match up to Sustiva- one of the most widely used fist line therapy drugs—casts a shadow for sure. However, a better understanding of the difference seen between people in the northern and southern hemispheres may change this perception. Additionally, some people may give greater weight to the lower toxicity levels seen with Selzentry and not base their treatment decisions solely on viral load.