HIV infection Infections and Infestations HIV infection
Conditions
Interventions
Patients randomised to the PI monotherapy group will stop other ART drugs and start/continue only on ritonavir-boosted PI monotherapy (selection of drug at discretion of physician or patient). Those w
Sponsors
Medical Research Council (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
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 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
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 after having achieved a viral load 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 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Loss of future drug options, defined as 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 study entry (i.e. excluding drug resistance that was known to be present on previous resistance testing). Duration of follow-up: 5 years (updated 12/09/2023: extended to 10 years, by amendment) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Serious drug or disease-related complication, defined as the first occurrence of one of the following in any individual patient: 1.1. Death from any cause 1.2. Serious AIDS-defining illness 1.3. Serious non-AIDS defining illness: 1.3.1. Acute myocardial infarction 1.3.2. Coronary artery disease requiring invasive procedures 1.3.3. Cirrhosis 1.3.4. Acute liver failure 1.3.5. End-stage renal disease 1.3.6. Stroke 1.3.7. Clinical acute pancreatitis 1.3.8. Severe lactic acidaemia 1.3.9. Severe facial lipoatrophy 1.3.10. Severe peripheral neuropathy 1.3.11. Non-AIDS malignancy 2. Adverse events, defined as the total number of Grade III and IV adverse events. 3. Virological rebound, defined in two ways using the "Time to Loss Of Virologic Response" (TLOVR) algorithm: 3.1. Two consecutive tests, taken at least 4 weeks apart, with a viral load more than 50 copies/ml (the first test must also be confirmed by re-testing the same blood sample). Patients who have virological rebound in the PI monotherapy arm, but re-suppress viral load to <50 copies/ml with re-introduction of NRTIs, will not count as failures; OR 3.2. As above, with at least one of the samples giving a viral load result more than 400 copies/ml. 4. CD4+ count change, defined as change from baseline in absolute CD4+ count. 5. Health-related Quality of Life change, defined as change from baseline in the mental and physical health summary scores. 6. Neurocognitive function change, defined as change from baseline in the neurocognitive function summary score. 7. Cardiovascular risk change, defined as change from baseline in the risk of cardiovascular disease calculated from the Framingham equation. 8. Health care costs, defined as the total cost of health care resources utilised per patient year. Duration of follow-up: 5 years | — |
Countries
England, United Kingdom
Outcome results
None listed