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

United Kingdom Research and Innovation (UKRI)

Status and phase: Unknown; Phase 4

Conditions: HIV Infection; Acquired Immunodeficiency Syndrome

Treatments: Drug: Standard-of-care Antiretroviral therapy; Drug: Protease Inhibitor

Study type: Interventional

Funder types: Other

Identifiers

NCT01230580

PIVOT

2007-006448-23 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 587 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

587 participants in 2 patient groups

Protease Inhibitor Monotherapy

Experimental group

Description:

Ritonavir-boosted protease inhibitor

Treatment:

Drug: Protease Inhibitor

Control

Active Comparator group

Description:

Standard-of-care triple-therapy regimen

Treatment:

Drug: Standard-of-care Antiretroviral therapy