Summary of drug interaction studies

Simon Collins, HIV i-Base

Several studies presented data on new drugs interactions. Some of these studies had been presented at earlier meetings, and the summary table of interactions from EACS, ICAAC and CROI, published in the April issue of HTB [1] may be a useful additional guide in association with those reported in the Table 1 below.

Table 1: PK and drug interaction studies at 7th Intl PK Workshop, Lisbon
ARV Interaction Results Recommendation Reference
Lopinavir/r 533mg/133mg BID Nevirapine 200mg bid at steady state LPV/r Ctrough maintained above minimum target in 14/15 PI/NNRTI naive patients, but wide interpatient variability Increasing LPV/r dose to 533/133 is appropriate with NVP.TDM is recommended. Data needed on new Meltrex formulation of Kaletra. Data needed on new Meltrex formulation of Kaletra. Else L et al. Abstract 67. [2]
TPV/r Methadone (single dose 5mg at TPV/r steady state) Methadone AUC, Cmax and C6H all decreased by ~50% ↓
(similar to other RTV- boosted PIs)
Dose of methadone may need to be increased Sabo JP et al. Abstract 42. [3]
Etravirine (TMC-125) Sildenafil (Viagra) 50mg dose at TMC-125 steady state Sildenafil AUC, & Cmax decreased by 43% & 55% ↓ and active metabolite reduced by 59% & 75% ↓
TMC-125 →
Dose administration of sildenafil should be tailored to individual response Schöller M et al. Abstract 45. [4]
TMC-278 (investigational NNRTI) Rifampicin TMC-278 AUC, Cmax and Cmin decreased by 80%, 69% & 89% ↓ TMC-278 and rifampicin should NOT be used together Van Heeswijk R et al. Abstract 74. [5]
TMC-278 (investigational NNRTI) Ketoconazole TMC-278 AUC, Cmax and Cmin increased by 49%, 30% & 76% ↑ Dose adjustment dependent on further studies. Van Heeswijk R et al. Abstract 74. [5]
Brecanavir/ ritonavir (300/100mg BD) Atazanavir 300mg once-daily All increased: Brecanavir by 38%, ritonavir by 56% and atazanavir by 44% Consider dose reduction of atazanavir. (Confirm with TDM) Ford S et al. Abstract 76. [6]


Unless stated otherwise, all references are to the Programme and Abstracts of the 7th International Workshop on Clinical Pharmacology of HIV Therapy, 20-22 April 2006, Lisbon. Available online at:

  1. Pharmacology and drug interaction studies in adults: summary table from CROI, ICAAC and EACS conferences. HIV Treatment Bulletin April 2006.
  2. Else L et al. The pharmacokinetics (PK) of lopinavir/ritonavir (LPV/r) 533/133 mg bid plus nevirapine (NVP) (200 mg bid) in adult HIV-1 infected individuals. Abstract 67.
  3. Sabo J et al. Stereoselective pharmacokinetics (PK) of methadone after coadministration with steady-state tipranavir/ritonavir 500/200 mg bid (TPV/r) in healthy volunteers. Abstract 42.
  4. Schöller, M et al. Effect of TMC125 on sildenafil pharmacokinetics Abstract 45.
  5. van Heeswijk R et al. The effects of CYP3A4 modulation on the pharmacokinetics of TMC278, an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI). Abstract 74.
  6. Ford S, Murray S, Anderson M et al. Brecanavir/ritonavir and atazanavir/ritonavir increased following repeat co-administration. Abstract 76.
  7. Moltó et al. The effect of ezetimibe (EZT) on the steady-state pharmacokinetics of lopinavir (LPV). Abstract 50.

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