Background:  Our objectives were to determine the difference in prevalence of single nucleotide polymorphisms (SNP) in the genes of P-gp and CYP3A isoenzymes in the various HIV-infected patient groups on antiretroviral therapy, and to investigate the association between SNP and abnormal drug levels.

Methods:  A population-based study with HIV-infected patients visiting the outpatient clinic was performed between March and June 2002. All consecutive HIV-infected patients treated with ART were eligible. They were identified and approached during regular outpatient clinic visits. Plasma samples were obtained on a routine basis for therapeutic monitoring. Nevirapine plasma concentrations were measured with reversed phase high performance liquid chromatography. Genotypic analysis was performed by polymerase chain reaction (PCR) technique. Standard descriptive statistical methods were used to describe population differences. All data were analysed with the Statistical Package for the Social Sciences (version 10.1 SPSS).

Results:  Of 371 patients treated with ART, 295 were eligible. The study group consisted of 69% males, 61% caucasians and 30% Blacks. Marked differences were observed in the prevalence of SNP between racial groups. Caucasians showed an allelic frequency of 49.7%, 5.9%, and 91.1% for the C3435T, CYP3A4*1B, and CYP3A5*3 alleles. Blacks, in contrast, showed an allelic frequency of 12.6%, 59.2%, and 28.1%. In persons with a CYP3A5*3 SNP the MDR-1 SNP C3435T was more prevalent (69% vs 42% in persons without CYP3A5*3). In individuals with a CYP3A4*1B the MDR-1SNP C3435T was less prevalent, compared with those without the CYP3A4*1B (32% vs 71%). Moreover, individuals with CYP 3A5*3 appeared to carry CYP3A4*1B less often than those without CYP3A5*3 (4% versus 73%). Of the 295 patients, 186 used NVP. None of the SNP were associated with low (<3.8 mg/L) NVP levels (n = 20), nor were gender or race. Similarly, there was no association between any of the SNP and high (>8.5 mg/L) NVP plasma levels (n = 19). We did however find a significant association between high NVP plasma levels and non-caucasian races. Positive hepatitis serology was associated with increased risk on high NVP plasma levels. 

Conclusion:  The differences in prevalence of SNP among caucasians and black HIV-infected subjects did not result in abnormal nevirapine plasma concentrations.

Keywords: nevirapine; snp; CYP3A