PIVOT study: protease inhibitor monotherapy

Note: the PIVOT study is now closed. Results were presented at CROI 2014 and the BHIVA/BASHH in 2014.

PIVOT stands for “Protease Inhibitor monotherapy Versus Ongoing Triple-therapy in the long term management of HIV infection”. The PIVOT study is the largest UK trial for fifteen years (since the Delta study) and includes over 40 sites in the UK and Ireland.

The trial will randomise at least 400 people to either continue their current treatment or switch to boosted-PI monotherapy, with follow-up out to five years.

To join the study, people need to have:

  • a CD4 count that is higher than 100 cells/mm3,
  • an undetectable viral load (less than 50 copies/mL) for more than 6 months, and
  • to be currently on a PI- or NNRTI-based triple therapy.

Patients who have previously had virological failure on a PI-containing regimen are excluded, but patients who have failed on an NNRTI-based regimen will be eligible if there is a resistance test available from the time of failure.

Additional exclusion criteria include:

  • a history of encephalopathy,
  • a high cardiovascular risk (>30%), or
  • uncontrolled hyperlipidaemia.

Choice of boosted PI is at the discretion of the individual doctor/patient but currently this would be expected to be lopinavir/r, darunavir/r, although neither are currently approved for this indication. Switching to alternative boosted-PIs is allowed within the study, as is therapeutic drug monitoring (TDM) to confirm trough levels are adequate in individual patients.

Viral rebound in patients on the monotherapy arm ( to >50 copies/mL on 2 consecutive tests, 4 weeks apart) prompts a return to triple therapy for the rest of the study.

The primary endpoint is the preservation of future treatment options defined by any change in a patients resistance profile. Secondary endpoints include serious drug or disease-related complications, tolerability, and changes in viral load, CD4, quality of life, neurocognitive function, cardiovascular risk, cost of healthcare. Sub-studies include drug exposure and viral suppression in compartments including genital tract and CSF.

Several studies have already looked at options for boosted-PI monotherapy, generally showing better results when used as a switch treatment after suppression to <50 copies/mL on a triple combination regimen. These studies, mainly using lopinavir/r monotherapy, have shown 25% of patients may fluctuate with low-level viraemia (50-500 copies/mL) but that did not result in PI resistance and is suppressed if RTIs are added back to the combination.

Recruitment started in May 2008, with at least 60 months follow-up.

Current status: Study finished, first results presented at CROI 2014.

This study is being run by the UK Medical Research Council (MRC).

Information on MRC website

For further details please contact: PIVOT@ctu.mrc.ac.uk