BREATHER (PENTA 16) Short-Cycle Therapy (SCT) (5 Days on/2 Days Off) in Young People With Chronic HIV-infection

NCT01641016 | Unknown Phase 2 DMC

• 2 other identifiers: BREATHER (PENTA 16)2009-012947-40
• Study Type: interventional
• Target: 160
• Locations: 8 countries
• Sites: 18

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.

Conditions

HIV

Keywords

short cycle therapy; young people; HIV

Outcome Measures

Primary Outcomes (1)

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

  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

  48 weeks

Secondary Outcomes (9)

• 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

Study Arms (2)

Continuous Therapy

ACTIVE COMPARATOR

Continue with current antiretroviral therapy regime as per standard care

Drug: efavirenz

Short Cycle Therapy

EXPERIMENTAL

Take current antiretroviral therapy 5 days a week (2 days off) as instructed by clinician

Drug: efavirenz

Interventions

efavirenz DRUG

May be taken as 600mg tablet, 200mg tablet or as part of a combination pill

Also known as: Trade name: Sustiva

Continuous Therapy; Short Cycle Therapy

Eligibility Criteria

• Age: 8 Years - 24 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• PENTA Foundation: lead
• Medical Research Council: collaborator
• ANRS, Emerging Infectious Diseases: collaborator

Study Sites (18)

St Jude Children's Research Hospital

Memphis, Tennessee, United States

Location

INSERM

Villejuif, France

Location

Universitätsklinikum Frankfurt

Frankfurt, Frankfurt Am Main, 60596, Germany

Location

Our Lady's Children's Hospital

Dublin, Ireland

Location

Program for HIV Prevention and Treatment (PHPT)/IRD 174

Changklan, Muang, Chiang Mai, 50100, Thailand

Location

HIV-NAT Thai Red Cross AIDS Research Centre

Bangkok, Thailand

Location

Joint Clinical Research Centre

Kampala, Uganda

Location

Kiev City AIDS Center

Kiev, Vidpochynku 11, 03115, Ukraine

Location

Birmingham Heartlands Hospital

Birmingham, United Kingdom

Location

University Hospital Bristol

Bristol, United Kingdom

Location

Leeds General Infirmary

Leeds, United Kingdom

Location

Leicester Royal Infirmary

Leicester, United Kingdom

Location

Evelina Children's Hospital

London, United Kingdom

Location

Great Ormond Street Hospital

London, United Kingdom

Location

Mortimer Market Centre

London, United Kingdom

Location

St George's Hospital

London, United Kingdom

Location

Nottingham University Hospital

Nottingham, United Kingdom

Location

John Radcliffe Hospital

Oxford, United Kingdom

Location

Related Publications (2)

• Turkova A, Moore CL, Butler K, Compagnucci A, Saidi Y, Musiime V, Nanduudu A, Kaudha E, Cressey TR, Chalermpantmetagul S, Scott K, Harper L, Montero S, Riault Y, Bunupuradah T, Volokha A, Flynn PM, Bologna R, Ramos Amador JT, Welch SB, Nastouli E, Klein N, Giaquinto C, Ford D, Babiker A, Gibb DM; BREATHER (PENTA 16) trial Group. Weekends-off efavirenz-based antiretroviral therapy in HIV-infected children, adolescents and young adults (BREATHER): Extended follow-up results of a randomised, open-label, non-inferiority trial. PLoS One. 2018 Apr 23;13(4):e0196239. doi: 10.1371/journal.pone.0196239. eCollection 2018.

  PMID: 29684092 DERIVED

• Bernays S, Paparini S, Seeley J, Namukwaya Kihika S, Gibb D, Rhodes T. Qualitative study of the BREATHER trial (Short Cycle antiretroviral therapy): is it acceptable to young people living with HIV? BMJ Open. 2017 Feb 17;7(2):e012934. doi: 10.1136/bmjopen-2016-012934.

  PMID: 28213595 DERIVED

Related Links

• Related Info

MeSH Terms

Interventions

efavirenz

Study Officials

• Karina M Butler, MRCPI

  Medical Research Council

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2012
• First Posted: July 16, 2012
• Study Start: April 1, 2011
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2016
• Last Updated: March 2, 2015

Record last verified: 2013-07

Locations

IE (1); TH (2); FR (1); DE (1); GB (10); UG (1); US (1); UA (1)