DSMB stops ACTG study due to suboptimal responses

An independent Data and Safety Monitoring Board (DSMB) has determined that the experimental, once-daily antiretroviral drug regimen of FTC (emtricitabine), atazanavir and ddI enteric-coated (ddI-EC) is inferior to a standard antiretroviral drug regimen and therefore should be discontinued in an ongoing clinical trial. The National Institute of Allergy and Infectious Diseases (NIAID), the part of the National Institutes of Health that oversees the trial, concurs with this recommendation and has stopped this component of the study.

This development arose from the DSMB’s recent review of safety and efficacy data from a Phase IV clinical trial sponsored by NIAID. The trial is examining whether certain regimens of antiretrovirals taken once a day are at least as good as a standard antiretroviral regimen containing a drug combination taken twice a day. The study involves 1,571 HIV-infected volunteers on four continents who were randomly assigned to take one of three drug regimens:

The DSMB found conclusive evidence that the second regimen, FTC + atazanavir + ddI-EC, is inferior to the control regimen primarily because it is less effective at controlling HIV. Based on this finding, the decision has been made to discontinue the emtricitabine + atazanavir + ddI-EC component of the study. All study participants are being notified of the development.

Comment

It is unclear why anyone would have expected FTC/ddI/un-boosted atazanavir to work as well as boosted – and what would be the advantage to someone risking this.

The press statement uses psuedo-medical language as if everything is so reasonable, eg “NIAID concurs with DSMB” – they have no choice and certainly couldn’t go against a DSMB recommendation; or using “conclusive evidence” rather than just say “the study found”.

More critically, the ddI and atazanavir interaction should have been sufficient for this not to have been studied – especially with unboosted atazanavir. It is also difficult to see how option 2 is a once-daily regimen if it required separating the ddI and atazanavir doses.

NIAID press release: Monitoring Board Recommends Stopping Experimental Treatment Regimen in International Study of Patients New to HIV Treatment.