A randomised controlled trial of a strategy of switching to boosted protease inhibitor monotherapy versus continuing combination antiretroviral therapy for the long-term management of HIV-1 infected patients who have achieved sustained virological suppression on highly-active antiretroviral therapy

Not Applicable

Completed

• Conditions: HIV infection; Infections and Infestations

• Registration Number: ISRCTN04857074
• Lead Sponsor: Medical Research Council (UK)

Brief Summary

2014 Results article in http://www.ncbi.nlm.nih.gov/pubmed/25078406 results 2015 Results article in http://www.ncbi.nlm.nih.gov/pubmed/26423649 results 2016 Results article in http://www.ncbi.nlm.nih.gov/pubmed/26986803 results 2016 Results article in http://www.ncbi.nlm.nih.gov/pubmed/27143662 results 2020 Results article in https://pubmed.ncbi.nlm.nih.gov/32202510/ sub-study results (added 24/03/2020) 2024 Results article in https://doi.org/10.1016/j.eclinm.2024.102457 8 year follow up (added 16/02/2024)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2008-02-01
• Study Completion: 2014-06-30
• Last Update Posted: 27 February 2024

Recruitment & Eligibility

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

Inclusion Criteria

1. Documented HIV infection on Enzyme-Linked Immuno-Sorbent Assay (ELISA) and confirmatory test.
2. Male or female patients, aged 18 years or more.
3. Receiving combination AntiRetroviral Therapy (ART) for at least 24 weeks with a regimen comprising 2 Nucleoside Reverse Transcriptase Inhibitor (NRTIs) and either an NonNucleoside Reverse Transcriptase Inhibitors (NNRTI) or a Protease Inhibitor (PI) (boosted or un-boosted).
4. No change in ART drugs in the 12 weeks prior to screening.
5. Plasma viral load <50 copies/ml for at least 24 weeks prior to screening (must have at least one documented result <50 copies/ml at more than 24 weeks prior to screening, and at least one documented result <50 copies/ml taken within 12 weeks prior to screening). A patient who has had one viral load blip to <200 copies/ml in the 24 weeks prior to screening may be included, provided that the two viral load tests that immediately preceded the blip and the two viral load tests that immediately followed the blip all gave results <50 copies/ml.
6. CD4+ count >100 cells/mm3 at screening.
7. Willing to continue unchanged or to modify antiretroviral therapy in accordance with the randomised assignment.
8. Likely to be resident in the UK for the full duration of the trial and willing to comply with trial visit schedule throughout the follow-up period.
9. Willing to provide written informed consent.

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. Evidence of previous failure while taking a PI-containing regimen (defined as failure to achieve viral load <50 copies/ml within 24 weeks after starting a PI-containing regimen, or having two viral load results >50 copies/ml after having achieved a viral load <50 copies/ml on the PI-containing regimen).
3. Evidence of previous failure on an NNRTI-containing regimen (defined as in 2, above), unless a successful viral sequence (resistance test) was obtained following failure and within 60 days prior to the date of switching to a new fully suppressive regimen.
4. Previous allergic reaction to a PI.
5. Patient currently using or likely to require use of concomitant medication with known interaction with PIs including rifampicin, amiodarone, flecainide, bupropion, clozapine, ergotamine, mexilitine, midazolam, pethidine, pimozide, quinidine, sertindole, sildenafil, voriconazole, zolpidem, St John's Wort.
6. Patient requiring treatment with radiotherapy, cytotoxic chemotherapy, or is anticipated to need these during the trial period.
7. Treatment for acute opportunistic infection within 3 months prior to trial screening.
8. Pregnant or trying to become pregnant at the time of trial entry.
9. 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.
10. History of HIV encephalopathy with current deficit >1 in any domain of the Neuropsychiatric AIDS Rating Scale.
11. Past or current history of cardiovascular disease, or 10-year absolute coronary heart disease risk of >30% (calculated from the Framingham equation, and assessed using the Joint British Societies cardiovascular risk prediction charts).
12. History of insulin-dependent diabetes mellitus.
13. Patient currently receiving interferon therapy for Hepatitis C virus infection or considered likely to need such therapy during the course of the trial.
14. Co-infection with hepatitis B, defined as Hepatitis BsAg positive at screening or at any time since HIV diagnosis.
15. Any other active clinically significant condition, or findings during screening medical history or examination that would, in the opinion of the investigator, compromise the patient's safety or outcome in the trial.
16. Anaemia (haemoglobin <9.5g/dl), neutropenia (absolute neutrophil count <1,000/mm3) or thrombocytopenia (platelet count <50,000mm3) at trial screening.
17. Alanine aminotransferase (ALT) or alkaline phosphatase greater than three times the upper limit of normal at trial screening.
18. Fasting plasma glucose >7.0mmol/L at trial screening.
19. Fasting plasma triglyceride level >3mmol/L at trial screening despite the use of lipid lowering drugs.
20. Fasting plasma total cholesterol >6.2mmol/L at trial screening despite the use of lipid lowering drugs.

Study & Design

• Study Type: Interventional
• Study Design: Not specified