An open randomised trial to evaluate different therapeutic strategies of combination therapy for human immunodeficiency virus (HIV-1) Infection

ISRCTN	ISRCTN44582462
DOI	https://doi.org/10.1186/ISRCTN44582462
Secondary identifying numbers	NA

Submission date: 06/09/2005
Registration date: 28/09/2005
Last edited: 10/07/2014

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

Study website

Contact information

Prof Abdel Babiker
Scientific

MRC CTU
222 Euston Road
London
NW1 2DA
United Kingdom

Study information

Study design	Randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Not specified
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title
Study acronym	INITIO
Study objectives	To compare in patients starting therapy for HIV infection, the activity of three strategies for using anti-retroviral regimens for at least 3 years in terms of the effects on CD4 cell counts, plasma HIV RNA, viral resistance, progression of HIV disease and survival.
Ethics approval(s)	Protocol approved in Belgium, Denmark, Finland, France, Germany, Ireland, Italy, Luxembourg, Portugal, Spain, Sweden, Switzerland, UK, Australia, New Zealand, Canada and Brazil.
Health condition(s) or problem(s) studied	HIV-1 infection
Intervention	Randomisation of approximately 1000 participants, from 17 countries worldwide, to one of three drug regimens: 1. 2 NRTIs plus a NNRTI 2. 2 NRTIs plus a PI 3. 2 NRTIs plus a NNRTI and PI Quality of life substudy: Quality of life questionnaires to be completed by participants consenting to this substudy in participating countries. Virology substudy: Participants joining this substudy at participating sites will have plasma and cells taken for storage for further study. Immunology substudy: Participants joining this substudy from specified clinics, within 6-hour delivery time of the centralised immunology labs in five countries, UK, France, Australia, Switzerland and Italy, will have additional blood samples taken for detailed lymphocyte phenotypes, lymphoproliferative assays and CD8 T-cell specific activity. In addition, a tetanus toxoid vaccination will be given at week 24 for research purposes. Lipodystrophy substudy: Participants for this substudy will be recruited from Australia and at baseline, every 12 weeks and at first therapeutic failure, a patient assessment of body changes, fasting insulin, C-Peptide, fibrogen and plasminogen activator inhibitor and exercise level assessment will be taken. At baseline, every 24 weeks and at therapeutic failure a record will be made of: DEXA scan, single cut abdominal computed tomography (CT) scan, standardised anthropometry and an electrocardiogram (ECG).
Intervention type	Other
Primary outcome measure	1. Change in CD4 cell count between 2 and 3 years 2. The proportion of patients with plasma HIV RNA below 50 copies/ml at 3 years
Secondary outcome measures	1. Change in CD4 cell count between 2 and 3 years 2. Change in plasma HIV RNA at 3 years 3. The time on first regimen 4. Time on second regimen (where applicable) 5. The time to first plasma HIV RNA below 50 copies/ml 6. Phenotypic and genotypic drug resistance at 3 years 7. Progression of HIV disease (including death)
Overall study start date	01/03/1999
Completion date	31/03/2001

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	1000
Key inclusion criteria	The participants in the trial must be HIV-1 infected, over 18 years of age, at any stage of HIV disease, but not acute symptomatic primary infection, where anti-retroviral therapy is indicated. Participants should be likely to take their first regimen for at least 6 months and be expected to adhere to the protocol.
Key exclusion criteria	1. The participants must not have received prior treatment with antiretroviral drugs or immunotherapy 2. There must be no history of peripheral neuropathy or pancreatitis 3. Individuals must not be receiving combination cytotoxic chemotherapy for cancer or parental therapy for an active opportunistic infection 4. Women should not be pregnant, breastfeeding or unwilling to use adequate contraception 5. Participants will be ineligible if biochemistry and haematology blood results from screening are outside the trial upper safety limits.
Date of first enrolment	01/03/1999
Date of final enrolment	31/03/2001

Locations

Countries of recruitment

Australia
Belgium
Brazil
Canada
Denmark
England
Finland
France
Germany
Ireland
Italy
Luxembourg
New Zealand
Portugal
Spain
Sweden
Switzerland
United Kingdom

Study participating centre

MRC CTU

London
NW1 2DA
United Kingdom

Sponsor information

Medical Research Council (UK)
Research council

20 Park Cresent
London
W1B 1AL
United Kingdom

"ROR"	https://ror.org/03x94j517

Funders

Funder type

Industry

The trial was supported with respect to funding, antiretroviral drugs, viral load assays and resistance assays by:

No information available

Dupont
Government organisation / For-profit companies (industry)

Alternative name(s): DuPont Company, E. I. du Pont de Nemours and Company, E. I. du Pont de Nemours & Company, EI du Pont de Nemours Company, E.I. du Pont de Nemours and Co., EI DuPont de Nemours & Co., E.I. Dupont De Nemours and Company, EI DuPont de Nemours and Company, Inc., DuPont de Nemours, Inc., EI duPont de Nemours, DuPont de Nemours
Location: United States of America

Hoffman-La Roche
Private sector organisation / For-profit companies (industry)

Alternative name(s): Hoffman-La Roche, F. Hoffmann-La Roche Ltd.
Location: Switzerland

Merck
Government organisation / For-profit companies (industry)

Alternative name(s): Merck & Co., Inc., Merck & Co.
Location: United States of America

Bristol Meyers Squibb

No information available

Medical Research Council
Government organisation / National government

Alternative name(s): Medical Research Council (United Kingdom), UK Medical Research Council, MRC
Location: United Kingdom

GlaxoSmithKline
Government organisation / For-profit companies (industry)

Alternative name(s): GlaxoSmithKline plc., GSK plc., GSK
Location: United Kingdom

Virco

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	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	22/07/2006		Yes	No