Concomitant intake of tenofovir disoproxil fumarate (TDF) does not impair plasma exposure of ritonavir (RTV) boosted atazanavir (ATV) in HIV-1 infected adults

Abstract

Background Recent data showed contradictory results on pharmacokinetic drug interactions of the protease inhibitor ATV and the nucleotide reverse transcriptase inhibitor TDF in HIV-1 infected adults. TDF co-administration decreases plasma levels of ATV 400mg QD alone, but has no impact on plasma trough levels of ATV 300mg QD when boosted with low-dose RTV. Methods We compared steady state plasma pharmacokinetics (PK) of ATV/RTV in a cohort of 53 (34male/19female) outpatients of comparable baseline characteristics, taking ATV/RTV 300/100mg QD+ 2–4 nucleoside reverse transcriptase inhibitors (NRTI) either with TDF (n=39) or without TDF (n=14). Following a standardized PK protocol, plasma drug levels were measured by LC/MS/MS after at least 4 weeks on the regimen prior to and 1,2,4,6,9,12,24h after drug intake. Noncompartmental AUCss, Cmin, Cmax and CLtot were subject to statistical analysis. Results see Table. Conclusions Co-administration of TDF does not impair the steady state plasma exposure of ATV or RTV in a limited number of HIV-1 infected patients. ATV/RTV 300/100mg+TDF/NRTI appears to be a pharmacokinetically suitable once-daily therapy regimen. Further clinical and PK data are obtained in this observational cohort. Clinical Pharmacology & Therapeutics (2005) 77, P18–P18; doi: 10.1016/j.clpt.2004.11.072 Table 1. ATV/RTV 300/100mg QD +NRTI with TDF mean (±SD) +NRTI without TDF mean (±SD) Mann-Whitney U-Test: p-value AUCss(ng24h/mL) ATV 40461 (±20824) 42193 (±19376) .68 RTV 11006 (±7623) 8774 (±3819) .55 Cmin(ng/mL) ATV 522 (±441) 663 (±444) .14 RTV 75 (±74) 61 (±35) .75 Cmax(ng/mL) ATV 3582 (±1877) 3772 (±2008) .86 RTV 1275 (±896) 1015 (±453) .39 CLtot(mL/min) ATV 174 (±127) 145 (±72) .67 RTV 231 (±161) 232 (±117) .57