Clinical trial NCT01230580: Protease Inhibitor Monotherapy Versus Ongoing Triple-therapy in the Long Term Management of HIV Infection (PIVOT)
Official title: A Randomised Controlled Trial of a Strategy of Switching to Boosted PI Monotherapy Versus Continuing Combination ART for the Long-term Management of HIV-1 Infected Patients Who Have Achieved Sustained Virological Suppression on HAART
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: HIV Infection
Acquired Immunodeficiency Syndrome
Keywords: Protease Inhibitors
RNA virus infections
Virus diseases
Sexually Transmitted Diseases viral
Immune system diseases
Anti-infective Agents
Drug resistance
Lead sponsor: Medical Research Council
Sponsor class: OTHER_GOV
Collaborators: name: NHS Health Technology Assessment Programme
First posted: 2010-10-29
Enrollment: 587
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The PIVOT trial aims to determine whether a strategy of switching to PI monotherapy is non-inferior to continuing triple-therapy, in terms of the proportion of patients who maintain all the drug treatment options that were available to them at baseline after at least 3 years of follow-up, and to compare clinical events, safety, toxicity and health economic parameters between the two strategies.


Eligibility criteria: Inclusion Criteria:

Vl \< 50 for 24 weeks prior to screening CD4 \> 100 at screening

Exclusion Criteria:

1. Known major protease resistance mutation(s) documented on prior resistance testing if performed (prior resistance testing is not mandatory for trial participation).
2. Previous change in ART drug regimen for reasons of unsatisfactory virological response (patients who have changed regimen for prevention or management of toxicity or to improve regimen convenience are permitted to enter the trial).
3. Previous allergic reaction to a PI.
4. Patient currently using or likely to require use of concomitant medication with known interaction with PIs.
5. Patient requiring treatment with radiotherapy, cytotoxic chemotherapy, or is anticipated to need these during the trial period.
6. Treatment for acute opportunistic infection within 3 months prior to trial screening.
7. Pregnant or trying to become pregnant at the time of trial entry.
8. History of active substance abuse or psychiatric illness that, in the opinion of the investigator, would preclude compliance with the protocol, dosing schedule or assessments.
9. History of HIV encephalopathy with current deficit \>1 in any domain of the Neuropsychiatric AIDS Rating Scale (see Appendix 7).
10. Past or current history of cardiovascular disease, or 10 year absolute coronary heart disease risk of \>30%, or risk of \>20% if the patient has diabetes or a family history of premature ischaemic heart disease or stroke.
11. History of insulin-dependent diabetes mellitus.
12. Patient currently receiving interferon therapy for Hepatitis C virus infection or planning to start treatment for Hepatitis C at the time of trial entry.
13. Co-infection with hepatitis B, defined as Hepatitis BsAg positive at screening or at any time since HIV diagnosis, unless the patient has had a documented Hepatitis B DNA measurement of less than 1000 copies/ml taken whilst off Hepatitis B active drugs.
14. Any other active clinically significant condition, or findings during screening medical history or examination, or abnormality on screening laboratory blood tests that would, in the opinion of the investigator, compromise the patient's safety or outcome in the trial.
15. Fasting plasma glucose \>7.0mmol/L at trial screening.

Primary outcomes:
measure: Loss of future drug options
timeFrame: Up to 5 years
Secondary outcomes:
measure: Death from any cause
timeFrame: Up to 5 years
measure: Serious AIDS-defining illness
timeFrame: Up to 5 years
measure: Serious non-AIDS defining illness
timeFrame: Up to 5 years
measure: Adverse events
timeFrame: Up to 5 years
measure: Confirmed Virological rebound
timeFrame: Up to 5 years
measure: CD4+ count change
timeFrame: Up to 5 years
measure: Health-related Quality of Life change
timeFrame: Up to 5 years
measure: Neurocognitive function change
timeFrame: Up to 5 years
measure: Cardiovascular risk change
timeFrame: Up to 5 years
measure: Health care costs
timeFrame: Up to 5 years
measure: HIV VL in Genital Secretions
timeFrame: Week 96
measure: HIV VL in CSF
timeFrame: Week 96
Other outcomes:
Locations:
Study officials:
affiliation: Medical Research Council
name: Nick Paton, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Winston A, Arenas-Pinto A, Stohr W, Fisher M, Orkin CM, Aderogba K, De Burgh-Thomas A, O'Farrell N, Lacey CJ, Leen C, Dunn D, Paton NI; PIVOT Trial Team. Neurocognitive function in HIV infected patients on antiretroviral therapy. PLoS One. 2013 Apr 30;8(4):e61949. doi: 10.1371/journal.pone.0061949. Print 2013.