A randomised controlled trial to assess the role of resistance assays in Human Immunodeficiency Virus (HIV) infection

ISRCTN	ISRCTN45898562
DOI	https://doi.org/10.1186/ISRCTN45898562
Protocol serial number	RDC01658
Sponsor	NHS R&D Regional Programme Register - Department of Health (UK)
Funder	NHS Executive London

Submission date: 23/01/2004
Registration date: 23/01/2004
Last edited: 19/04/2007

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr David Dunn
Scientific

MRC Clinical Trials
222 Euston Road
London
NW1 2DA
United Kingdom

Phone	+44 (0)20 7670 4739
Email	d.dunn@ctu.mrc.ac.uk

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Scientific title
Study acronym	ERA - Evaluation of Resistance Assays
Study objectives	The main hypothesis is that providing genotypic resistance assays improves the treatment of HIV-infected individuals who are not highly treatment-experienced. A subsidiary hypothesis is that phenotypic plus genotypic resistance testing is superior to genotypic resistance testing alone in HIV-infected individuals who are highly treatment-experienced. The ERA trial was designed to assess the clinical utility of HIV resistance testing in patients who had failed therapy and whose most recent viral load was at least 2000 copies/ml. Patients were randomised to one of two parts, depending on whether the clinician was able (Part A) or was not able (Part B) to select a regimen of 3 or more drugs that, with reasonable expectation, had potent anti-HIV activity and to which each drug contributed. Patients in Part A were allocated to (a) no resistance test, or (b) a centralised genotypic assay (VIRCOGENTM). All participants in Part B had the VIRCOGENTM assay and were randomised to have or not have in addition a centralised phenotypic assay (ANTIVIROGRAMTM). Patients allocated to resistance testing had access to testing at any time during follow-up when clinically indicated, according to the original allocation.
Ethics approval(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	Infection and infestations: HIV/Acquired Immunodeficiency Syndrome (AIDS)
Intervention	1. Standard care 2. Access to a centralised genotypic assay with computer assisted interpretation 3. Access to a centralised phenotypic assay
Intervention type	Other
Primary outcome measure(s)	Plasma HIV-1 RNA at 12 months measured centrally at the Royal Free Hospital using the Roche ultra-sensitive assay (with a lower limit of detection of 50 copies/ml).
Key secondary outcome measure(s)	1. CD4 count at 12 months (all laboratories participate in the UK National Quality Assessment Scheme of SD4) 2. Antiretroviral treatment prescribed including the number of switches in therapy and drugs used (constructed from 3-monthly case record forms) 3. Adherence with antiretroviral treatment prescribed (assessed by a 3-monthly self-completed questionnaire) 4. Available drug options (as assessed by genotypic resistance) at 12 months 5. Progression to a new AIDS-defining events will be collected retrospectively on an annual basis after 12 months to enable long-term benefits to be assessed
Completion date	01/08/2002

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Not Specified
Target sample size at registration	480
Key inclusion criteria	1. Confirmed HIV-positive 2. Age 18 years or more 3. Expected to live at least 12 months 4. Able to give informed consent 5. Currently receiving antiretroviral therapy 6. Most recent HIV ribonucleic acid (RNA) >2000 copies/ml 7. Clinician and patients have decided to change therapy on the basis of virological failure 8. Clinician considers that a resistance test may influence selection of new drug regimen, and clinician and patient are prepared to wait for the result (up to 1 month) before changing treatment
Key exclusion criteria	1. Naive to antiretroviral drugs or previous exposure to 1 or 2 nucleoside analogue reverse transcriptase inhibitors only 2. Part A only: a resistance test (genotypic or phenotypic) had previously been performed or patient would have had a local resistance test 3. Part B only: a phenotypic resistance test had previously been performed 4. Participation in certain trials of antiretroviral therapies, considered on a case-by-case basis 5. Was unlikely to comply with routine schedule of visits
Date of first enrolment	01/02/2000
Date of final enrolment	01/08/2002

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

MRC Clinical Trials

London
NW1 2DA
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	Results	15/04/2005		Yes	No