Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Protease inhibitor monotherapy for long-term management of HIV infection: A randomised, controlled, open-label, non-inferiority trial
The Lancet HIV, Volume 2, No. 10, Year 2015
Notification
URL copied to clipboard!
Description
Background: Standard-of-care antiretroviral therapy (ART) uses a combination of drugs deemed essential to minimise treatment failure and drug resistance. Protease inhibitors are potent, with a high genetic barrier to resistance, and have potential use as monotherapy after viral load suppression is achieved with combination treatment. We aimed to assess clinical risks and benefi ts of protease inhibitor monotherapy in long-term clinical use: in particular, the eff ect on drug resistance and future treatment options. Methods In this pragmatic, parallel-group, randomised, controlled, open-label, non-inferiority trial, we enrolled adults (=18 years of age) positive for HIV attending 43 public sector treatment centres in the UK who had suppressed viral load (<50 copies per mL) for at least 24 weeks on combination ART with no change in the previous 12 weeks and a CD4 count of more than 100 cells per μL. Participants were randomly allocated (1:1) to maintain ongoing triple therapy (OT) or to switch to a strategy of physician-selected ritonavir-boosted protease inhibitor monotherapy (PI-mono); we recommended ritonavir (100 mg)-boosted darunavir (800 mg) once daily or ritonavir (100 mg)-boosted lopinavir (400 mg) twice daily, with prompt return to combination treatment if viral load rebounded. All treatments were oral. Randomisation was with permuted blocks of varying size and stratifi ed by centre and baseline ART; we used a computer-generated, sequentially numbered randomisation list. The primary outcome was loss of future drug options, defi ned as new intermediate-level or high-level resistance to one or more drugs to which the patient's virus was deemed sensitive at trial entry (assessed at 3 years; non-inferiority margin of 10%). We estimated probability of rebound and resistance with Kaplan-Meier analysis. Analyses were by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Number registry, number ISRCTN04857074. Findings Between Nov 4, 2008, and July 28, 2010, we randomly allocated 587 participants to OT (291) or PI-mono (296). At 3 years, one or more future drug options had been lost in two participants (Kaplan-Meier estimate 0.7%) in the OT group and six (2.1%) in the PI-mono group: diff erence 1.4% (-0.4 to 3.4); non-inferiority shown. 49 (16.8%) participants in the OT group and 65 (22.0%) in the PI-mono group had grade 3 or 4 clinical adverse events (diff erence 5.1% [95% CI -1.3 to 11.5]; p=0.12); 45 (six treatment related) and 56 (three treatment related) had serious adverse events. Interpretation Protease inhibitor monotherapy, with regular viral load monitoring and prompt reintroduction of combination treatment for rebound, preserved future treatment options and did not change overall clinical outcomes or frequency of toxic eff ects. Protease inhibitor monotherapy is an acceptable alternative for long-term clinical management of HIV infection. © Paton et al. Open Access article published under the terms of CC BY.
Authors & Co-Authors
Paton, Nicholas I.J.
United Kingdom, London
Medical Research Council
Singapore, Singapore City
National University of Singapore
Stöhr, Wolfgang
United Kingdom, London
Medical Research Council
Arenas-Pinto, Alejandro
United Kingdom, London
Medical Research Council
United Kingdom, London
University College London
Fisher, Martin J.
United Kingdom, Wakefield
Nhs England
Williams, Ian G.
United Kingdom, London
University College London
Johnson, Margaret A.
United Kingdom, London
The Royal Free Hospital
Orkin, Chloë M.
United Kingdom, Wakefield
Nhs England
Chen, Fabian
United Kingdom, Reading
Royal Berkshire Hospital
Winston, Alan
United Kingdom, London
St Mary's Hospital
Gompels, Mark M.
United Kingdom, Bristol
Southmead Hospital Bristol
Fox, Julie
United Kingdom, London
Guy's and st Thomas' Nhs Foundation Trust
Scott, Karen
United Kingdom, London
Medical Research Council
Dunn, David T.
United Kingdom, London
Medical Research Council
Fisher, Martin J.
United Kingdom, Brighton
Elton John Centre
Clarke, Amanda E.
United Kingdom, Brighton
Elton John Centre
Johnson, Margaret A.
United Kingdom, London
The Royal Free Hospital
Williams, Ian T.
United Kingdom, London
University College London
Pellegrino, Pierre
United Kingdom, London
University College London
Haddow, Lewis J.
United Kingdom, London
University College London
Hand, James
United Kingdom, London
Barts and the London School of Medicine and Dentistry
de Souza, Carl B.S.S.
United Kingdom, London
Barts and the London School of Medicine and Dentistry
Howe, Rawleigh Craig
United Kingdom, Manchester
Manchester Royal Infirmary
Gompels, Mark M.
United Kingdom, Bristol
Southmead Hospital Bristol
Beeching, Nicholas J.
United Kingdom, Liverpool
Royal Liverpool University Hospital
Fox, Julie Meriel
United Kingdom, London
Guy's and st Thomas' Nhs Foundation Trust
Wilkins, Edmund G.L.
United Kingdom, Manchester
North Manchester General Hospital
Brook, Michael Gary
United Kingdom, London
Central Middlesex Hospital
Chadwick, David Robert
United Kingdom, Middlesbrough
The James Cook University Hospital
Read, Sarah W.
United Kingdom, Plymouth
Derriford Hospital
Herieka, Elbushra Ali Mohamed
United Kingdom, Bournemouth
Royal Bournemouth Hospital
Hay, Phillip E.
United Kingdom, London
St George's Hospital
Ong, Edmund Liang Chai
Unknown Affiliation
Martin, Karen
Unknown Affiliation
Dockrell, D. Harold
United Kingdom, Sheffield
Royal Hallamshire Hospital
Ainsworth, Jonathan G.
United Kingdom, London
North Middlesex University Hospital
Kegg, Stephen
Unknown Affiliation
Taylor, Stephen Charles
United Kingdom, Birmingham
Heartlands Hospital
Gazzard, Brian G.
United Kingdom, London
Chelsea and Westminster Hospital
Rowlands, Jane
United Kingdom, London
Chelsea and Westminster Hospital
Allan, Sris P.
United Kingdom, Coventry
University Hospital Coventry
O\'Farrell, N.
United Kingdom, Southall
Ealing Hospital
Martin, Fabiola
United Kingdom, Harrogate
Harrogate District Hospital
Bennett, Charles Lee
United Kingdom, Harrogate
Harrogate District Hospital
Kapembwa, Moses Silungwe
United Kingdom, Harrow
Northwick Park Hospital
Post, Frank A.
United Kingdom, London
King's College Hospital
Campbell, Lucy J.
United Kingdom, London
King's College Hospital
Palfreeman, Adrian J.
United Kingdom, Leicester
Leicester Royal Infirmary
Balachandran, Thambiah
United Kingdom, Luton
Luton and Dunstable University Hospital
Kakowa, Memory
United Kingdom, Luton
Luton and Dunstable University Hospital
O'Connell, Rebecca
United Kingdom, London
Newham University Hospital
Lacey, Charles J. N.
Unknown Affiliation
Russell-Sharpe, Sarah
Unknown Affiliation
Leen, Clifford L.S.
United Kingdom, Edinburgh
Western General Hospital
Morris, Sheila
United Kingdom, Edinburgh
Western General Hospital
David, Neal
United Kingdom, Norwich
Norfolk and Norwich University Hospitals Nhs Foundation Trust
Paton, Nicholas
United Kingdom, London
Medical Research Council
Dunn, David T.
United Kingdom, London
Medical Research Council
Fleck, Sue L.
United Kingdom, London
Medical Research Council
Martins, Sheila Ouriques
United Kingdom, London
Medical Research Council
Owen-Powell, Ellen
United Kingdom, London
Medical Research Council
White, Ellen
United Kingdom, London
Medical Research Council
Statistics
Citations: 78
Authors: 61
Affiliations: 40
Identifiers
Doi:
10.1016/S2352-3018(15)00176-9
ISSN:
23523018
Research Areas
Environmental
Genetics And Genomics
Health System And Policy
Infectious Diseases
Study Design
Randomised Control Trial