{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T20:10:50Z","timestamp":1772050250158,"version":"3.50.1"},"reference-count":100,"publisher":"National Institute for Health and Care Research","issue":"21","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.nationalarchives.gov.uk\/doc\/non-commercial-government-licence\/non-commercial-government-licence.htm"}],"funder":[{"DOI":"10.13039\/501100000664","name":"Health Technology Assessment programme","doi-asserted-by":"publisher","award":["06\/403\/90"],"award-info":[{"award-number":["06\/403\/90"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Health Technol Assess"],"abstract":"<jats:sec id=\"abs1-1\"><jats:title>Background<\/jats:title><jats:p>Standard-of-care antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection uses a combination of drugs, until now considered essential to minimise treatment failure and development of drug resistance. Protease inhibitors (PIs) are potent with a high genetic barrier to resistance and have the potential for use as monotherapy after viral load (VL) suppression achieved on combination therapy. However, longer-term resistance and toxicity risks are uncertain.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-2\"><jats:title>Objective<\/jats:title><jats:p>To compare the effectiveness, toxicity profile and cost-effectiveness of PI monotherapy with those of standard-of-care triple therapy in a pragmatic long-term clinical trial.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-3\"><jats:title>Design<\/jats:title><jats:p>Open-label, parallel-group, randomised controlled trial.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-4\"><jats:title>Setting<\/jats:title><jats:p>Forty-three HIV clinical centres in the UK NHS.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-5\"><jats:title>Participants<\/jats:title><jats:p>HIV-positive adults taking standard combination ART with a suppressed VL for \u2265\u20096 months.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-6\"><jats:title>Interventions<\/jats:title><jats:p>Patients were randomised to maintain ongoing triple therapy (OT) or switch to a strategy of physician-selected ritonavir-boosted PI monotherapy (PI-mono), with prompt return to combination therapy in the event of VL rebound.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-7\"><jats:title>Main outcome measures<\/jats:title><jats:p>The primary outcome was reduction of future drug options, defined as new intermediate-\/high-level resistance to one or more drugs to which the patient\u2019s virus was considered to be sensitive at trial entry (non-inferiority comparison, 10% margin). Secondary outcomes included confirmed virological rebound, serious drug- or disease-related complications, total grade 3 or 4 adverse events (AEs), neurocognitive function change, cluster of differentiation 4 (CD4) cell count change, change in health-related quality of life, cardiovascular risk change, health-care costs and health economic analysis.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-8\"><jats:title>Results<\/jats:title><jats:p>In total, 587 participants were randomised (77% male, 68% white) to OT (<jats:italic>n<\/jats:italic>\u2009=\u2009291) or PI-mono (<jats:italic>n<\/jats:italic>\u2009=\u2009296) and followed for a median of 44 months, of whom 2.7% withdrew\/were lost to follow-up. One or more episodes of confirmed VL rebound were observed in eight patients (Kaplan\u2013Meier estimate 3.2%) in the OT group and 95 patients (35.0%) in the PI-mono group [absolute risk difference 31.8%, 95% confidence interval (CI) 24.6% to 39.0%;<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001]. PI-mono patients who changed to ART after VL rebound all resuppressed (median 3.5 weeks). The proportions with loss of a future drug option at 3 years were 0.7% in the OT group and 2.1% in the PI-mono group (difference 1.4%, (95% CI \u20130.4% to 3.4%); non-inferiority demonstrated). There were no significant differences in serious disease complications between groups or in the frequency of grade 3 or 4 clinical AEs (16.8% OT group vs. 22% PI-mono group; absolute risk difference 5.1%, 95% CI \u20131.3% to 11.5%;<jats:italic>p<\/jats:italic>\u2009=\u20090.12). Overall, the PI-mono strategy was shown to be cost-effective compared with OT under most scenarios explored. PI-mono was cost saving because of the large savings in ART drug costs while being no less effective in terms of quality-adjusted life-years in the within-trial analysis and only marginally less effective when extrapolated to lifetime outcomes.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-9\"><jats:title>Conclusions<\/jats:title><jats:p>PI monotherapy, with prompt reintroduction of combination therapy for VL rebound, was non-inferior to combination therapy in preserving future treatment options and is an acceptable and cost-effective alternative for long-term management of HIV infection.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-10\"><jats:title>Trial registration<\/jats:title><jats:p>Current Controlled Trials ISRCTN04857074.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-11\"><jats:title>Funding<\/jats:title><jats:p>This project was funded by the NIHR Health Technology Assessment programme and will be published in full in<jats:italic>Health Technology Assessment<\/jats:italic>; Vol. 20, No. 21. See the NIHR Journals Library website for further project information.<\/jats:p><\/jats:sec>","DOI":"10.3310\/hta20210","type":"journal-article","created":{"date-parts":[[2016,3,18]],"date-time":"2016-03-18T10:18:41Z","timestamp":1458296321000},"page":"1-158","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["The Protease Inhibitor Monotherapy Versus Ongoing Triple Therapy (PIVOT) trial: a randomised controlled trial of a protease inhibitor monotherapy strategy for long-term management of human immunodeficiency virus infection"],"prefix":"10.3310","volume":"20","clinical-trial-number":[{"clinical-trial-number":"isrctn04857074","registry":"10.18810\/isrctn","type":"results"}],"author":[{"given":"Nicholas I","family":"Paton","sequence":"first","affiliation":[{"name":"Medical Research Council Clinical Trials Unit at University College London, Institute of Clinical Trials and Methodology, University College London, London, 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