The identification of
children and adolescents at risk of poor recovery is important for the timely
restart of treatment. The researchers therefore aimed to investigate factors
that might predict improved immunological recovery after restarting treatment. They
hypothesised that these may include age and nadir CD4%.

Data from paediatric
HIV-positive cohorts were pooled. Children under 18 years of age on ART for
more than six months before a treatment interruption of 30 or more days were
included. CD4 percentage at the restart of ART and in the long-term (up to 24
months after restarting ART) after the first treatment interruption was
modelled.

From a total of 7358 children
on ART, 779 with at least one treatment interruption were included in the
analysis.

Unplanned treatment interruptions continue to
occur in children and young people. 

The median age at first
treatment interruption was 10.1 years (IQR: 6.4-13.6) after being on ART for
5.5 years. The median treatment interruption was 9.0 months (IQR: 3.5-22.5).  

The primary reason for
treatment interruption was the patient’s decision and/or non-compliance (49%),
followed by treatment failure (22%), doctor’s decision (17%) and side-effects
(9%).

A third had more than one
treatment interruption. The second, third and fourth treatment interruptions happened
at 13.8, 14.8 and 15.8 years of age, respectively.

The children had a relatively
good immunological status at the first treatment interruption with a mean CD4 percentage
of 27.3% (standard deviation 11%). However, only 27% had a suppressed viral
load ( 400 copies/mL).

At the end of treatment
interruption the mean CD4 percentage was 19.2% (95% CI: 18.3-20.1%). Two years after
restarting ART, it rose to 27.1% (95% CI: 26.2-27.9%), therefore reaching the
pre-treatment interruption value, with half the increase in the first six
months.

This may support findings
from the CHER and PENTA 11 trials suggesting that treatment interruption may be
a safe choice with regular CD4 monitoring, even if not routinely recommendable.

However, multivariable
analysis from this real-world setting shows several factors affecting recovery
after treatment interruption.

Children under three years of
age at the first treatment interruption had the highest CD percentage at restart of
treatment and in the long-term (up to 24 months). After adjusting for CD4 percentage
during treatment interruption, CD4 percentage recovery was highest in the youngest
children, suggesting that older children have a decreased ability to
reconstitute CD4 cells.

Long-term CD4 percentage
recovery after restarting ART was highest among those with a treatment
interruption of less than three months, those who restarted ART after the year
2000 and those with a CD4 percentage nadir of 25% or more (all, p 0.001).

In general, a lower CD4 percentage
during the treatment interruption was associated with poorer immunological
recovery after restarting and in the long term. Nonetheless, children with a
CD4 percentage nadir 15% during treatment interruption whose viral load had
previously been suppressed reached a better long term CD4 percentage than those with a
detectable viral load. Viral load had no effect on recovery in children with CD4 percentage nadir ≥ 25%.

The authors caution that while
young children show potential for good recovery, CD4 monitoring during
treatment interruption is critical so that treatment is restarted before there
are any significant decreases in CD4 cell count.