Clinical trial NCT01641016: BREATHER (PENTA 16) Short-Cycle Therapy (SCT) (5 Days on/2 Days Off) in Young People With Chronic HIV-infection
Official title: BREATHER (PENTA 16) Short-Cycle Therapy (SCT) (5 Days on/2 Days Off) in Young People With Chronic HIV-infection
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: HIV
Keywords: short cycle therapy
young people
HIV
Lead sponsor: PENTA Foundation
Sponsor class: NETWORK
Collaborators: name: Medical Research Council
name: ANRS, Emerging Infectious Diseases
First posted: 2012-07-16
Enrollment: 160
Sex: ALL
Minimum age (years): 8
Maximum age (years): 24
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

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.
timeFrame: 48 weeks
Secondary outcomes:
measure: HIV-1 RNA <50 c/ml at 24 and 48 weeks
timeFrame: 24 and 48 weeks
measure: Number of HIV mutations present at week 4, 12, 24, 36 or 48 conferring resistance to drugs taken at randomisation or during the tria
timeFrame: Weeks 4, 12, 24, 36, 48
measure: Change in CD4 (absolute and percentage) from randomisation to 24 and 48 weeks
timeFrame: 24 and 48 weeks
measure: Change in ART (defined as any change from the ART regimen at randomisation)
timeFrame: 48 weeks
measure: Grade 3 or 4 clinical and laboratory adverse events
timeFrame: 48 weeks
measure: ART treatment modifying adverse events (all grades)
timeFrame: 48 weeks
measure: New CDC stage B or C diagnosis or death
timeFrame: 48 weeks
measure: Changes in fasting glucose, cholesterol, triglycerides, LDL, HDL and VLDL levels through 48 weeks
timeFrame: 48 weeks
measure: Adherence, acceptability, and quality of life over 48 weeks as assessed by patient completed questionnaires
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Memphis
country: United States
facility: St Jude Children's Research Hospital
state: Tennessee
city: Villejuif
country: France
facility: INSERM
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt
state: Frankfurt am Main
city: Dublin
country: Ireland
facility: Our Lady's Children's Hospital
city: Changklan, Muang
country: Thailand
facility: Program for HIV Prevention and Treatment (PHPT)/IRD 174
state: Chiang Mai
city: Bangkok
country: Thailand
facility: HIV-NAT Thai Red Cross AIDS Research Centre
city: Kampala
country: Uganda
facility: Joint Clinical Research Centre
city: Kiev
country: Ukraine
facility: Kiev City AIDS Center
state: Vidpochynku 11
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Bristol
country: United Kingdom
facility: University Hospital Bristol
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: London
country: United Kingdom
facility: Evelina Children's Hospital
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
city: London
country: United Kingdom
facility: Mortimer Market Centre
city: London
country: United Kingdom
facility: St George's Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospital
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
Study officials:
affiliation: Medical Research Council
name: Karina M Butler, MRCPI
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.