BREATHER (PENTA 16) Short-Cycle Therapy (SCT) (5 Days on/2 Days Off) in Young People With Chronic HIV-infection
- Registration Number
- NCT01641016
- Lead Sponsor
- PENTA Foundation
- Brief Summary
The overall aim of the BREATHER trial is to evaluate the role of Short-Cycle Therapy (SCT) in the management of HIV-infected young people who have responded well to antiretroviral therapy (ART) and to determine whether young people with chronic HIV infection undergoing Short-Cycle Therapy of five days on ART and two days off maintain the same level of viral load suppression as those on continuous therapy, over 48 weeks.
To assess the advantages and disadvantages of the strategy, the incidence of toxicities, immunological control, resistance mutations, acceptability, quality of life and adherence to the randomised strategy will also be compared.
Importantly, because of insufficient data on short-term viral load rebound after stopping ART in this population, the trial will incorporate an initial pilot phase in selected centres, to assess the safety of the SCT strategy by evaluating detailed HIV-1 RNA profiles of participants on the SCT strategy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 160
- HIV-1 infected young people aged 8 to 24 years inclusive (Young people recruited between the ages of 16-21 must either be in regular physical contact with their clinician or be able to transfer to an adult physician at the same site for follow-up or to an affiliated adult site).
- Parents/carers and/or young people, where applicable, willing to provide informed consent.
- On a stable first-line ART treatment containing at least 2 NRTIs/NtRTIs and EFV for at least 12 months and willing to continue the regimen throughout the study period. Young people on regimens containing nevirapine (NVP) or a boosted protease inhibitor with undetectable viral load for over one year who wish to enrol should switch to EFV. Once they are stable on the EFV containing regimen for more than 12 weeks they may be enrolled (must have 2 subsequent HIV-1 RNA measurements <50 c/ml over a minimum period of 12 weeks). Previous dual therapy and/or substitution of NRTIs is allowed providing any changes were not for disease progression, immunological or virological failure (where virological failure is defined as two successive HIV-1 RNA results>1000 c/ml) subsequent to virological control having been achieved on ART.
- Viral suppression (HIV-1 RNA <50 c/ml) for at least the prior 12 months (at least the last 3 measurements, including screening): young people who have experienced a single viral load >50 but <1000 copies/ml (preceded and followed by VL<50 c/ml) in the last 12 months can be enrolled.
- CD4 cell count ≥350 106/L at screening visit.
- Centre must routinely use an assay which detects HIV RNA-1 viral load ≥50 c/ml.
- Pregnancy or risk of pregnancy in females of child bearing potential.
- Acute illness (young people may be enrolled after illness).
- Receiving concomitant therapy for an acute illness (young people may be enrolled after finishing therapy).
- A creatinine, AST or ALT of grade 3 or above at screening.
- On a regimen including nevirapine or a boosted PI (young people may switch to an EFV based regimen).
- Previous ART monotherapy (except for the prevention of mother-to-child transmission)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Continuous Therapy efavirenz Continue with current antiretroviral therapy regime as per standard care Short Cycle Therapy efavirenz Take current antiretroviral therapy 5 days a week (2 days off) as instructed by clinician
- Primary Outcome Measures
Name Time Method HIV-1 RNA ≥50 copies/ml (confirmed on a separate sample within 1 week) at any of week 4, 12, 24, 36 or 48. 48 weeks This outcome measure only considers HIV-1 RNA measurements at these time points due to the difference in viral load monitoring in the pilot phase and the main trial. However if a young person enrolled in the pilot phase has HIV-1 RNA ≥50 copies/ml at weeks 1, 2 or 3 (reproducible on the same sample) or at week 8 (confirmed on the same sample within 1 week), they will be considered as reaching the primary outcome at week 4 and 12 respectively
- Secondary Outcome Measures
Name Time Method HIV-1 RNA <50 c/ml at 24 and 48 weeks 24 and 48 weeks Number of HIV mutations present at week 4, 12, 24, 36 or 48 conferring resistance to drugs taken at randomisation or during the tria Weeks 4, 12, 24, 36, 48 Change in CD4 (absolute and percentage) from randomisation to 24 and 48 weeks 24 and 48 weeks Change in ART (defined as any change from the ART regimen at randomisation) 48 weeks Grade 3 or 4 clinical and laboratory adverse events 48 weeks ART treatment modifying adverse events (all grades) 48 weeks New CDC stage B or C diagnosis or death 48 weeks Changes in fasting glucose, cholesterol, triglycerides, LDL, HDL and VLDL levels through 48 weeks 48 weeks Adherence, acceptability, and quality of life over 48 weeks as assessed by patient completed questionnaires 48 weeks
Trial Locations
- Locations (18)
Our Lady's Children's Hospital
🇮🇪Dublin, Ireland
Program for HIV Prevention and Treatment (PHPT)/IRD 174
🇹ðŸ‡Changklan, Muang, Chiang Mai, Thailand
INSERM
🇫🇷Villejuif, France
St Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
Universitätsklinikum Frankfurt
🇩🇪Frankfurt, Frankfurt am Main, Germany
HIV-NAT Thai Red Cross AIDS Research Centre
🇹ðŸ‡Bangkok, Thailand
Kiev City AIDS Center
🇺🇦Kiev, Vidpochynku 11, Ukraine
Birmingham Heartlands Hospital
🇬🇧Birmingham, United Kingdom
University Hospital Bristol
🇬🇧Bristol, United Kingdom
Evelina Children's Hospital
🇬🇧London, United Kingdom
Leicester Royal Infirmary
🇬🇧Leicester, United Kingdom
Leeds General Infirmary
🇬🇧Leeds, United Kingdom
Great Ormond Street Hospital
🇬🇧London, United Kingdom
St George's Hospital
🇬🇧London, United Kingdom
Mortimer Market Centre
🇬🇧London, United Kingdom
John Radcliffe Hospital
🇬🇧Oxford, United Kingdom
Nottingham University Hospital
🇬🇧Nottingham, United Kingdom
Joint Clinical Research Centre
🇺🇬Kampala, Uganda