HIV Positive Teens May Need Modified Atazanavir Dose

HIV positive adolescents taking boosted atazanavir (Reyataz) may reach higher plasma concentrations of the drug with corresponding higher bilirubin levels than adult patients, according to results from a small Spanish study published in the January 2011 Journal of Adolescent Health. These findings suggest that teens may benefit from drug level monitoring and perhaps reducing their atazanavir doses below the level recommended for adults.

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.


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.



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.