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Week-on, weekend-off treatment controls viral load in young people
Keith Alcorn, 2015-02-25 17:00:00
Taking an efavirenz-based
antiretroviral regimen during the week and taking no medication on two days
over the weekend was just as effective as daily treatment in controlling viral
load in an 11-country trial conducted among adolescents and young people, Professor
Karina Butler of Our Lady’s Children’s
Hospital, Dublin, Ireland, reported at the Conference on Retroviruses and Opportunistic
Infections (CROI 2015) in Seattle, USA, on Tuesday.
Sustaining adherence to daily treatment appears to be more difficult in
young people and adolescents. Studies of adherence show consistently that older
age is strongly correlated with better adherence, and clinicians in Europe,
North America and sub-Saharan Africa have reported the difficulties faced by
adolescents in taking medication regularly.
“As paediatric treaters we’re desperate for new ways of supporting
adherence,” Dr Elaine Abrams of Columbia University, New York, told a press
conference reviewing the study results.
The BREATHER study was designed to test a regimen that could normalise
life for young people, said Prof. Butler.
“Adolescents going out at the weekend often don’t take their medication
because they don’t want people to see them taking it,” she said. The prospect
of lifelong therapy is also daunting for many young people.
“The priniciple of this study was quite different [from treatment
interruption studies in which], you were allowing viral rebound, whereas in
this study you were taking a break from taking medication,” Prof. Butler told
the press conference.
Interrupting treatment for prolonged periods is not recommended; a
large international study called SMART found that people who interrupted
treatment had a higher risk of death and serious illness, both AIDS-related and
non-AIDS related. Studies of shorter periods of
treatment interruption, of fixed duration, have also shown
that stopping treatment for a month or week at a time results in a higher risk
of viral rebound.
However, the durability of a five days on/two days off regimen has not
been tested in a large trial, and it is plausible that treatment based on drugs
which take a long time to clear from the blood, such as efavirenz, would be
less likely to result in viral rebound if doses are missed on two consecutive
days, provided that viral load has already been suppressed for a prolonged
period. A study in 221 patients found
that after one year of viral suppression, the risk of viral rebound declined
substantially in people who were not fully adherent to treatment.
The BREATHER study recruited 199 young people between the ages of 8 and 24
(median age 14) in Europe, Uganda, Thailand, Argentina and the United States.
Twenty-one per cent were aged 18 or over. Young people were eligible to join the study if they
had been on stable antiretroviral therapy with viral load below 50 copies/ml
for 12 months, and if they had never experienced viral rebound. Participants
were randomly assigned to receive 'short cycle' treatment, during which they
took two consecutive days off treatment each week (usually Saturday and
Sunday), or continuous treatment.
After a median of 85 weeks of follow up, viral load had rebounded above
50 copies/ml in six of the short cycle group and seven of the continuous
The weekend-off regimen proved highly acceptable to young people, with
74% saying that it made life a 'lot' easier, although when questioned about a
range of everyday activities that might be difficult as a result of treatment,
the only area of statistically significant improvement was “going out with
friends”. Participants who stopped treatment at the weekend said that side-effects lessened at the weekend, and were also more prone to report previously
Participants in the weekend-off arm were less likely to change
treatment for reasons of toxicity or simplification during the study, but there
was no significant difference in the reporting of adverse events related to
Experts stressed that these results should be treated with caution, and
that young people should not begin missing weekend doses until longer-term
follow up of the participants in this study has provided reassurance that the
strategy is safe. In particular, they stressed that the results apply only to
young people taking efavirenz-based treatment who had undetectable viral
load and no previous history of viral rebound.
Young people who took part in the study expressed concern
that others might try doing the same thing without proper monitoring and end up
“It’s important to highlight that they were a very select group of
suppressed patients,” said Dr Elaine Abrams of Columbia University, New York.
“It’s important to say that they had never failed treatment before.
They were the best group of individuals to enter such a study,” agreed Dr
Butler. Many adolescents with a long history of HIV treatment are likely to
have experienced several episodes of viral rebound, leading to the development
of drug resistance. Lower levels of antiretrovirals during the weekend off
treatment might not be sufficient to suppress drug-resistant virus in those
young people with a history of multiple treatment failures, leading to viral
rebound and further drug resistance.
“I don’t think results of this study should impact on clinical
practice. Clearly we need to look at long-term follow up to see that it is
safe,” said Dr Butler.
However, she went on, “if there are individual circumstances a
clinician may choose to change treatment, with careful monitoring.”