High bilirubin levels may be more frequent in adolescents taking the protease inhibitor
atazanavir (Reyataz) than in adults, Spanish
investigators warn in the Journal of
Elevated bilirubin can lead to the development of a
side-effect called hyperbilirubinaemia,
which involves a yellowing of the skin and eyes. It is not dangerous, but the
investigators warn that its impact on appearance means that it should be taken
seriously, especially when it occurs in adolescents.
“Physical appearance influences a major part of the
self-esteem of an adolescent and so a symptom like jaundice can lead to body
dissatisfaction and social adjustment problems because of visible physical
Atazanavir is widely used for the treatment of HIV-positive
adults. Its standard dose is 300mg, which is taken with a 100mg ritonavir (Norvir) booster. Good results have been
achieved using atazanavir in treatment-naïve and treatment-experienced
authorities approved the drug for use by children and adolescents in 2010. However,
data on the use of atazanavir by younger patients are still limited. Between
2002 and 208 a research team in Madrid undertook a study of plasma
concentrations of antiretroviral drugs in HIV-positive children and
adolescents. As part of their investigations they monitored blood
concentrations of atazanavir and bilirubin.
A total of 129 patients were included in the study, five of
whom were taking ritonavir-boosted atazanavir. All were female, and were being
treated with a night time atazanavir/ritonavir dose of 300/100mg. The patients had a median age of
Although the investigators believe that it was “remarkable”
that all the atazanavir-treated patients were female, they nevertheless note
that there is no evidence that gender affects response to the drug.
Over the course of the study 16 paired blood samples
monitoring atazanavir and bilirubin levels were obtained from the patients. The
blood samples were drawn a mean of 13 hours after dosing with atazanavir.
The patients had a mean atazanavir concentration of 14740.6
ng/ml. This was slightly lower than the concentration of 2000 ng/ml observed after
a similar interval in adults in separate research.
As expected, concentrations of bilirubin were significantly
higher in the adolescents treated with atazanavir than those taking alternative
antiretrovirals (2 mg/dl vs. 0.47 mg/dl, p = 0.001).
There was also variability in levels of bilirubin among the
five individuals taking atazanavir. Mean bilirubin levels were 1.5 mg/dl among those
with an atazanavir concentration below 2000 ng/ml. However, bilirubin levels
were significantly higher for patients with drug concentrations above this
level (mean, 3.1 mg/dl, difference, p = 0.018).
Analysis showed that there was a significant correlation
between bilirubin concentrations and higher blood levels of atazanavir (p =
However, the investigators noted that hyperbilirubinaemia
was associated with only “mild” jaundice, and they emphasise that no patient
stopped taking atazanavir because of this side-effect.
“The preliminary findings of this study show that
adolescents with regimens including atazanavir present higher bilirubin levels
more frequently as compared with other patients,” comment the investigators.
They believe that their findings have implications for the
care and monitoring of young people taking this drug, and write: “Plasma
measurements of atazanavir could be useful in monitoring atazanavir toxicity
for selected patients with elevated unconjugated bilirubin or jaundice.”