Short-Cycle Therapy (SCT) (5 days on/2 days off) in young people with chronic HIV infection
Can HIV-infected children and young people taking efavirenz as one of their anti-HIV medicines take weekends off from their treatment?
What was this study about?
BREATHER is a study comparing two different ways for children and young people with HIV to take anti-HIV (antiretroviral) medicines when one of their treatments is a medicine called efavirenz:
1) Taking the medicines every day (as is usual).
2) Taking the medicines during the week for 5 days and then having a break for 2 days (i.e. no anti-HIV medicines) at the weekend.
This second way of taking the medicines is called Short Cycle Therapy (SCT).
The BREATHER study also asked children and young people for their views about these different ways of taking anti-HIV medicines. This study looked at how easy it is for children and young people to stick to each of the treatments and what influences them to take their medicines regularly. This part of the BREATHER study was carried out by the London School of Hygiene and Tropical Medicine.
The study also examined adherence to treatment and assessed the quality of life of the children and young people taking part.
What difference did this study make?
During the main study, most young people continued to have very low levels of HIV virus in their blood, whether taking anti-HIV medicines daily or following the SCT strategy. There was no evidence to suggest that more drug resistance developed as a result of taking drugs the medicines as SCT, and the number of side effects reported was similar in both groups of participants. Young people reported that they valued having weekends off treatment.
Whilst the initial results were exciting, participants were only followed up for one year. To check that the SCT strategy is a viable option over a longer period of time, the trial was extended for a further 2 years, with nearly all young people agreeing to join the extension study.
The extended follow-up results show no difference between young people in the continuous therapy group and those in the short cycle therapy group in terms of how well the virus was kept under control. This confirms the earlier findings.
Most of those young people on the short cycle therapy arm, who experienced any increase in the amount of virus in their blood, had the virus under control again (undetectable) without having to change their drugs, once they returned to taking their drugs every day (ie. back to continuous therapy). Young people themselves were involved in designing dissemination messages about the trial. While the size of the trial has meant that results are not definitive enough to change guidelines, young people have shown considerable interest in the results and have called for more research in this area, including through workshops undertaken by WHO to discuss gaps in research for adolescents. Economic analyses of BREATHER trial results have also shown that the approach is cost saving.
The BREATHER results have led to the development of a larger trial looking at Short Cycle Therapy among young people living with HIV in sub-Saharan Africa. This larger trial is called BREATHER Plus. BREATHER Plus is using the drug dolutegravir rather than efavirenz. It will find out whether Short Cycle Therapy is a safe and effective approach for young people living in places where routine viral load monitoring is carried out less frequently than in BREATHER.
Type of study
Who funded the study?
The NIHR Health Technology Assessment Programme (UK Dept of Health) funded this study in the UK and Ireland. The PENTA Foundation funded the study in other countries that took part.
When did it take place?
The main trial opened to recruitment in 2011 and was fully recruited in 2013. The results of the main trial were published in 2015. Patients were followed up until July 2016.
Where did it take place?
The trial took place in hospital clinics in UK and Ireland, as well as other European countries, the United States, Argentina, Thailand, Brazil and Uganda.
Who was included?
199 children and young people aged between 8 and 24 years from Europe, Thailand, Uganda, Argentina and the USA. These young people were all currently taking anti-HIV medicines and had a very low level of virus in their blood.