Entry criteria changed for Optima study and treatment options for salvage therapy
Simon Collins, HIV i-Base
Optima (OPTions for Management with Antiretrovirals) is an international collaboration between the Veterans Administration in the USA, CIHR in Canada and the MRC in the UK.
The study looks at two key questions in multi-drug experienced patients on a failing regimen: whether there is a benefit to a treatment interruption prior to adoption of a new regimen, and the possible additional benefit from using more than 4 drugs in a salvage setting. After a resistance test, patients are randomised to either an immediate treatment change or to a drug free period (ideally three months, but flexible depending on individual patient response). They are also randomised to using up to 4 drugs (NOT including small doses of ritonavir if used as a PK booster for a second PI) or to a Mega-ART regimen using at least 5 drugs. Investigational and expanded access drugs are allowed within the Optima protocol, and can be added as they become available.
Several important changes have now been made that broaden the entry criteria:
- Failure of at least two regimens including drugs from each of the three drug classes have been broadened to include evidence of resistance from a resistance test, even if these drugs have never been used by a patient. This now covers people infected with drug resistant HIV or those with cross-resistance.
- the upper cut-off for entry to the study has been raised from 200 cells/mm3 to 300 cells/mm3
- reducing the viral load entry criteria to 2500* copies/ml (from 5,000-10,000 copies/ml )
The previous exclusion of patients with a history of low adherence has now been dropped.
* by Roche Amplicor Monitor/COBAS v1.5 (<50 cut-off assay), or Bayer v3.0/Chiron v3.0 bDNA ‘ultrasensitive’ assays; or to >5000 copies using the older Roche Amplicor, v 1.0.
Twelve UK sites are currently enrolling patients include Belfast, Cambridge, Edinburgh, Oxford, Sheffield, Brighton, Colchester, Peterborough and in London (at the Chelsea and Westminster, St Marys, Central Middlesex and the Royal Free Hospitals). With a further ten sites soon to receive approval.
Enquiries from doctors wishing to run this study at their hospital should be made to Douglas Newberry, trial manager for Optima at the MRC Clinical Trials Unit on 020 7670 4813 (email@example.com)
General information is also available on the trial website:
These changes are welcomed as they open the study to patients at an earlier stage of treatment failure, and before the CD4 count has fallen too low. Optima is a management study, with a large degree of flexibility in individually managing patient care in this difficult population.
Choice of individual drugs, including changes of drugs over time (as long as the intention is to keep to the allocation of either ‘up to 4 drugs’ or ‘5 or more drugs’) and flexibility to extend or reduce the period of treatment interruption, all remain with the individual patient/doctor. Where more frequent monitoring is preferred this is also possible (although funded as part of the study).
It is hoped that accurate targeting of suitable patients will answer these important questions in a timely manner.