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Genes Affect HIV Drug Levels, Hyperbilirubinemia Risk

Variants affect plasma atazanavir and risk of developing hyperbilirubinemia

TUESDAY, Jan. 2 (HealthDay News) -- Variants of two genes can affect plasma levels of atazanavir as well as the risk of developing severe hyperbilirubinemia in HIV-infected patients taking atazanavir and ritonavir, according to the results of a study published in the Jan. 2 issue of AIDS.

Vincent Soriano, M.D., Ph.D., and colleagues from Hospital Carlos III in Madrid, Spain, examined polymorphisms in the uridin-glucoronosyl-transferase 1A1 (UGT1A1) and multidrug resistance 1 (MDR1) genes, which can affect plasma concentrations of bilirubin and atazanavir, respectively. They studied 118 HIV-infected patients taking atazanavir and ritonavir.

The researchers found that 32 percent of patients had the MDR1-3435 CC genotype, and they had higher minimum atazanavir concentrations than patients with the CT or TT genotypes. There was an independent association between having at least one T allele at this position and lower atazanavir plasma concentrations.

The investigators also found that 80 percent of patients with grade 3-4 hyperbilirubinemia had the UGT1A1 7/7 genotype and 29 percent had the 6/7 genotype. There was an independent association between having at least one 7 allele and severe hyperbilirubinemia (odds ratio 2.96).

"Polymorphisms at MDR1-3435 significantly influence atazanavir plasma concentrations, as does being Caucasian patients with CT/TT genotypes, having lower atazanavir levels, even using ritonavir boosting," Soriano and colleagues conclude. "On the other hand, although atazanavir plasma concentrations directly correlate with bilirubin levels, the risk of severe hyperbilirubinemia is further increased in the presence of the UGT1A1-TA7 allele."

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