Atazanavir
is generally well-tolerated and is less likely than other
HIV protease inhibitors
to cause blood lipid abnormalities and other metabolic side
effects. However, it interferes with processing of bilirubin
-- a pigment by-product of the normal breakdown of red blood
cells -- resulting in hyperbilirubinemia, or elevated plasma
bilirubin levels. This is usually not clinically harmful,
but the resulting jaundice (yellowing of the skin and eyes)
leads some patients to discontinue the drug.
Ana
Nso from Hospital Infantil La Paz in Madrid and colleagues
conducted a study looking at atazanavir use among vertically
infected adolescents who were taking at least their third
antiretroviral therapy (ART) regimen due to multiple previous
treatment failure -- showing that atazanavir is commonly used
as a "rescue drug" in this population, the researchers
noted.
"Physical
appearance influences a major part of the self-esteem of an
adolescent and a symptom like jaundice can lead to body dissatisfaction
and social adjustment problems because of visible physical
differences," they added.
The analysis included 5 participants taking atazanavir as
part of a combination ART regimen, selected from a cohort
of 129 HIV positive adolescents. All were female and at least
12 years of age (median 15.5 years).
Participants
took 300 mg atazanavir boosted with 100 mg ritonavir once-daily,
usually at night. The investigators measured morning atazanavir
plasma concentrations -- 12 to 13 hours after drug administration
-- during regular outpatient visits. A total of 16 samples
were collected and analyzed.
Results
 |
"
All the tested samples had atazanavir concentrations higher
than the recommended 24-hour concentration of 150 ng/mL
derived from studies of adults. |
|
However,
the mean atazanavir concentration among the adolescents
was 1474 ng/mL -- slightly lower than the 2000 ng/mL seen
in adults 12-13 hours after receiving the same drug dose. |
|
There
was considerable variability in plasma concentrations
among individual patients, with a broad range of values.
|
|
As
expected, the average bilirubin level was significantly
higher among teens taking atazanavir compared with those
using other drugs (2.0 vs 0.47 mg/dL, respectively). |
|
Among
participants taking atazanavir, those with higher drug
concentrations had significantly higher bilirubin levels: |
|
 |
Mean
total bilirubin level was 1.5 mg/dL among patients
with plasma atazanavir levels < 2000 ng/mL. |
|
Mean
total bilirubin was about twice as high, at 3.1
mg/dL, among patients with plasma atazanavir concentrations
> 2000 ng/mL. |
|
|
Participants
with hyperbilirubinemia had only mild jaundice, however,
and none required treatment discontinuation for this reason.
|
|
None
of the participants showed evidence of atazanavir drug-resistance
mutations. |
Based
on these preliminary findings, the study authors concluded,
"adolescents with regimens including atazanavir present
higher bilirubin levels more frequently as compared with the
other patients."
Therefore,
they added, "plasma measurements of atazanavir levels
could be useful in monitoring atazanavir toxicity, for selected
patients with elevated unconjugated bilirubin or jaundice."
Investigator affiliations: Servicio de Pediatria, Hospital
Infantil La Paz, Madrid, Spain; Laboratorio de Inmuno-Biologìa
Molecular, Hospital General Universitario "Gregorio Maranon,"
Madrid, Spain; Servicio de Pediatria-Infecciosas, Hospital
Universitario "Carlos III," Madrid, Spain; Servicio
de Pediatria-Infecciosas, Hospital de Getafe, Madrid, Spain;
Servicio de Pediatria-Infecciosas, Hospital Universitario
"Doce de Octubre," Madrid, Spain; Servicio de Pediatria-Infecciosas,
Hospital General Universitario "Gregorio Maranon,"
Madrid, Spain; Unidad Asociada de Retrovirologìa Humana,
HGUGM-CSIC, Madrid, Spain.
1/21/11
Reference
AP Nso, B Larru, JM Bellon, and others. HIV-infected adolescents:
relationship between atazanavir plasma levels and bilirubin
concentrations. Journal of Adolescent Health 48(1): 100-102
(Free
full text). January 2011.
