BACKGROUND:Human immunodeficiency virus (HIV)-infected individuals show large interindividual variation in response to antiretroviral therapy. Efavirenz (EFV) and nevirapine (NVP) are nonnucleoside... Show moreBACKGROUND:Human immunodeficiency virus (HIV)-infected individuals show large interindividual variation in response to antiretroviral therapy. Efavirenz (EFV) and nevirapine (NVP) are nonnucleoside reverse transcriptase inhibitors, which are prescribed in combination with other antiretroviral therapy in so-called highly active antiretroviral therapy. Recent studies provide evidence for the role of cytochrome P450 (CYP) genes, in particular CYP2B6, in relation to EFV and NVP pharmacokinetics. In this study, the authors investigated whether common ABCB1, CYP2A6, CYP2B6, CYP2D6, and CYP3A5 alleles are associated with plasma concentrations of EFV and NVP in HIV-infected individuals. METHODS:Plasma drug concentrations were quantified by high-performance liquid chromatography in 143 HIV-infected individuals receiving either EFV or NVP. Genotyping for common alleles was performed by restriction fragment length polymorphism and Taqman assays. Individuals were genotyped for 11 single-nucleotide polymorphisms in 5 genes. CYP2B6 haplotypes were reconstructed by PHASE. RESULTS:Plasma EFV concentrations were positively associated with CYP2B6 c.516G>T, c.785A>G, and c.983A>G single-nucleotide polymorphisms in HIV-infected individuals. Increased plasma concentrations of EFV and NVP were present in individuals with the CYP2B6*6/*6 or *6/*18 haplotype compared with CYP2B6*1/*1 [increase of 62% (95% confidence interval, 44.0-80.1) and 24% (95% confidence interval, 7.0-40.0), respectively, P < 0.01]. No significant association with other genes in relation to EFV or NVP concentrations was found. CONCLUSIONS:In this study, a strong association of CYP2B6*6 and CYP2B6*18 alleles in relation to EFV and NVP plasma concentrations was found, which confirmed previous studies. Show less
HIV-infected travellers frequently use atovaquone/ proguanil as malaria prophylaxis. We compared atovaquone/ proguanil pharmacokinetics between healthy volunteers and HIV-infected patients taking... Show moreHIV-infected travellers frequently use atovaquone/ proguanil as malaria prophylaxis. We compared atovaquone/ proguanil pharmacokinetics between healthy volunteers and HIV-infected patients taking efavirenz, lopinavir/ ritonavir or atazanavir/ritonavir. The geometric mean ratio (95% confidence interval) area under the curve (AUC)(0 -> t) for atovaquone relative to the healthy volunteers was 0.25 (0.16-0.38), 0.26 (0.17-0.41) and 0.54 (0.350.83) for patients on efavirenz, lopinavir/ ritonavir and atazanavir/ ritonavir, respectively. Proguanil plasma concentrations were also significantly lower (38-43%). Physicians should be alert for atovaquone/ proguanil prophylaxis failures in patients taking efavirenz, lopinavir/ ritonavir or atazanavir/ ritonavir. Show less
