<qa>  How many subjects will be screened to enroll a total of 63 healthy volunteers?The expression of P-glycoprotein, a transporter protein present in enterocytes as well as other cells involved in the absorption and distribution of HIV protease inhibitors, has been linked to a single nucleotide polymorphism SNP in exon 26 of the MDR1 gene, C3435T. Individuals homozygous for the T allele have reduced P-gp expression compared to CC individuals. Preliminary studies by other investigators to determine the influence of MDR1 genotype on HIV protease inhibitor pharmacokinetics have yielded inconclusive results. The primary purpose of this study is to determine the relationship, if any, between MDR1 genotypes and plasma concentrations of the HIV protease inhibitors indinavir and saquinavir. Secondary objectives of this investigation will 1 assess the relationship between CYP3A4 activity and indinavir and saquinavir exposure and 2 characterize the relationship, if any, between P-gp expression on lymphocyte surfaces and MDR1 genotype. Up to 150 subjects will be screened to enroll a total of 63 healthy volunteers 21 subjects each in the CC, TT, and CT groups. Each subject will have blood drawn for P-gp expression analysis and MDR1 genotyping at screening. Next, subjects will receive oral midazolam 8 mg for CYP3A4 phenotyping; a single blood sample will be collected 4 hours after midazolam administration for determination of midazolam and 1-hydroxymidazolam. Between 7 and 28 days after midazolam administration, subjects will receive indinavir 800 mg every 8 hours for one day and a single 800 mg dose the next morning dose 4. Between 7 and 28 days after indinavir administration, subjects will receive saquinavir soft-gel capsules 1200 mg three times daily for 3 days and a single dose on the morning of day 4 dose 10. Post-dose blood samples will be collected over 8 hours following dose 4 of indinavir and dose 10 of saquinavir. Indinavir and saquinavir pharmacokinetic parameters primarily AUC and Cmax will be compared across MDR1 genotype groups using ANOVA with post-hoc testing. 1-hydroxymidazolam: midazolam ratios will be correlated to indinavir and saquinavir AUCs as well as compared across MDR1 genotype groups. P-gp expression on lymphocyte surfaces will be determined by flow cytometry, quantified, and compared across MDR1 genotype groups. Data from this investigation will determine whether MDR1 genotype influences protease inhibitor plasma concentrations. 