Protease Inhibitor Monotherapy Versus Ongoing Triple-therapy in the Long Term Management of HIV Infection (PIVOT)

Phase 4

• Conditions: HIV Infection; Acquired Immunodeficiency Syndrome
• Interventions: Drug: Protease Inhibitor; Drug: Standard-of-care Antiretroviral therapy

• Registration Number: NCT01230580
• Lead Sponsor: Medical Research Council

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2008-11
• Status Verified: 2010-10
• Study First Submitted: 2010-10-27
• Study First Submitted QC: 2010-10-28
• Study First Posted: 2010-10-29
• Last Update Submitted: 2012-10-09
• Last Update Posted: 2012-10-10
• Primary Completion: 2013-11
• Study Completion: 2013-11

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 587

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Protease Inhibitor Monotherapy	Protease Inhibitor	Ritonavir-boosted protease inhibitor
Control	Standard-of-care Antiretroviral therapy	Standard-of-care triple-therapy regimen

Primary Outcome Measures

Name	Time	Method
Loss of future drug options	Up to 5 years	The first occurrence of intermediate to high level resistance to any one or more of the standard antiretroviral drugs (limited to licensed drugs in contemporary use) to which the patient's virus was considered to be sensitive at trial entry (i.e. excluding drug resistance that was known to be present on previous resistance testing).

Secondary Outcome Measures

Name	Time	Method
Serious AIDS-defining illness	Up to 5 years
Adverse events	Up to 5 years
Death from any cause	Up to 5 years
Serious non-AIDS defining illness	Up to 5 years
Confirmed Virological rebound	Up to 5 years
CD4+ count change	Up to 5 years
Neurocognitive function change	Up to 5 years
Health care costs	Up to 5 years
HIV VL in Genital Secretions	Week 96	In a sub-set of participants (n=73):-; * Compare prevalence of detectable VL and magnitude of viral replication in genital secretions in patients taking PI monotherapy and triple therapy; to test if PI monotherapy is non-inferior to triple therapy.; * Compare drug levels in genital secretions and plasma.; * Describe the profile of drug resistance (if any) in patients with detectable VL in genital secretions and to compare this with any previous or subsequent resistance profile in plasma.; (Genital Secretions substudy REC # 09/H0305/58)
HIV VL in CSF	Week 96	In a subset of participants on PI monotherapy (n=40).; * Estimate the proportion of patients who have detectable HIV viral load in CSF after 48 weeks on PI monotherapy, and to refute the hypothesis that this proportion is greater than 20%.; * Assess whether CSF markers of CNS immune activation, inflammation and neuronal degeneration are elevated after 48 weeks on PI monotherapy.; * Assess whether CSF HIV viral load and markers of immune activation, inflammation and neuronal degeneration are elevated in patients with symptomatic CNS disease.; (CNS substudy REC # 09/H0305/58).
Cardiovascular risk change	Up to 5 years
Health-related Quality of Life change	Up to 5 years