Overview

This trial is active, not recruiting.

Condition hiv
Treatment efavirenz
Phase phase 2/phase 3
Sponsor PENTA Foundation
Collaborator Medical Research Council
Start date April 2011
End date June 2014
Trial size 160 participants
Trial identifier NCT01641016, 2009-012947-40, BREATHER (PENTA 16)

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
Continue with current antiretroviral therapy regime as per standard care
efavirenz Trade name: Sustiva
May be taken as 600mg tablet, 200mg tablet or as part of a combination pill
(Experimental)
Take current antiretroviral therapy 5 days a week (2 days off) as instructed by clinician
efavirenz Trade name: Sustiva
May be taken as 600mg tablet, 200mg tablet or as part of a combination pill

Primary Outcomes

Measure
HIV-1 RNA ≥50 copies/ml (confirmed on a separate sample within 1 week) at any of week 4, 12, 24, 36 or 48.
time frame: 48 weeks

Secondary Outcomes

Measure
HIV-1 RNA <50 c/ml at 24 and 48 weeks
time frame: 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
time frame: Weeks 4, 12, 24, 36, 48
Change in CD4 (absolute and percentage) from randomisation to 24 and 48 weeks
time frame: 24 and 48 weeks
Change in ART (defined as any change from the ART regimen at randomisation)
time frame: 48 weeks
Grade 3 or 4 clinical and laboratory adverse events
time frame: 48 weeks
ART treatment modifying adverse events (all grades)
time frame: 48 weeks
New CDC stage B or C diagnosis or death
time frame: 48 weeks
Changes in fasting glucose, cholesterol, triglycerides, LDL, HDL and VLDL levels through 48 weeks
time frame: 48 weeks
Adherence, acceptability, and quality of life over 48 weeks as assessed by patient completed questionnaires
time frame: 48 weeks

Eligibility Criteria

Male or female participants from 8 years up to 24 years old.

Inclusion Criteria: - 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. Exclusion Criteria: - 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)

Additional Information

Official title BREATHER (PENTA 16) Short-Cycle Therapy (SCT) (5 Days on/2 Days Off) in Young People With Chronic HIV-infection
Principal investigator Karina M Butler, MRCPI
Trial information was received from ClinicalTrials.gov and was last updated in February 2015.
Information provided to ClinicalTrials.gov by PENTA Foundation.