Major change to OPTIMA salvage therapy study in the UK

The OPTIMA study has recently received MREC approval for a significant amendment to the trial design. This makes this a more appealing study for both patients and doctors.

Previously, patients were required to enter a two way randomisation both for whether or not to take a treatment interruption prior to changing to a new salvage regimen and for whether to use less than or more than five drugs in their upcoming combination.

The amendment now allows the patient to choose one of these previously randomised factors, and only requires randomisation for the remaining question.

Low recruitment to the original study was partly a result of a lower pool of eligible patients, but also partly because of strong feelings either for or against treatment interruptions or multi-drug therapy.

There is however little reliable evidence for the benefits or risks for these approaches, with small studies indicating conflicting results, even in the short term for a treatment interruption. Similarly, early studies using mega-HAART (with five or more drugs) are complicated by both sensitivity to drugs and drug exposure and obtaining therapeutic drug levels.

This study now presents a very safe option for patients. Choice of drugs is left to the individual patient and physician, and resistance testing is available to aid this. Additionally, ritonavir, if used as a booster to another PI, is not included within the standard regimen arm (not Mega-HAART), in practice allowing use of five drugs in the reduced drug arm. Therapeutic drug monitoring is already available in the UK for patients on salvage therapy and, as with all decisions for routine clinical care, this is managed by the patient’s regular doctor. Similarly, although the study protocol suggests a treatment interruption of 12 weeks, this can be reduced to eight weeks (as suggested by the positive results from the French Giga-HAART study) or extended for a longer period, depending on the individual patient response.

OPTIMA is a tri-national multicentre collaboration between the MRC in the UK, the Veterans Association in the US and the Canadian Trials Network in Canada. The study amendment is only available for patients in the UK.