Lack of effect of doxycycline on trough concentrations of protease inhibitors or non-nucleoside reverse transcriptase inhibitors in HIV-infected patients

HIV Clin Trials. 2013 Nov-Dec;14(6):313-8. doi: 10.1310/hct1406-313.

Abstract

Background: Many HIV-treated patients travel to malaria-infected zones, but very few data are available on potential interactions between antiretroviral and antimalarial drugs.

Method: We performed a pharmacokinetic study on the interaction of doxycycline (100 mg/d) on 2 protease inhibitors (PIs), atazanavir and lopinavir, and 2 non-nucleoside reverse transcriptase inhibitors (NNRTIs), efavirenz and nevirapine, given at usual daily doses in HIV-infected migrants native from sub-Saharan Africa included in the VIHVO ANRS-study before travelling to a sub-Saharan country. Antiretroviral trough plasma concentrations were measured at enrollment visit during the month preceding the travel before doxycycline introduction and on the week following the patients' return to France when they had been taking doxycycline for at least 15 days. Impact of doxycycline on antiretroviral concentrations was tested either with antiretroviral drugs separately or within the therapeutic classes (PI or NNRTI) in patients with an HIV RNA level <50 copies/mL at both visits and with good declared adherence. The Two One-Sided Test that was adapted to the Wilcoxon test was used to evidence the lack of interaction. Sixty-five patients receiving regimens containing atazanavir (n = 1), ritonavir-boosted atazanavir (n = 14), ritonavir-boosted lopinavir (n = 23), efavirenz (n = 17), nevirapine (n = 10) were included.

Results: Lack of pharmacokinetic interaction was statistically significant when tested by therapeutic class (PI, P = .02; NNRTI, P = .005) and was not demonstrated for each antiretroviral when tested separately.

Conclusion: This study is the first to assess the interaction of doxycycline on PI and NNRTI. This lack of pharmacokinetic interaction supports the choice of doxycycline as the antimalarial drug in patients treated with PI or NNRTI.

Keywords: antiretroviral drug; cohort; doxycycline; interaction; malarial drug; pharmacokinetic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / blood
  • Anti-HIV Agents / pharmacokinetics*
  • Antimalarials / pharmacokinetics*
  • Doxycycline / pharmacokinetics*
  • Drug Interactions
  • HIV Infections / drug therapy
  • HIV Infections / metabolism
  • Humans
  • Malaria / prevention & control
  • Protease Inhibitors / blood
  • Protease Inhibitors / pharmacokinetics*
  • Reverse Transcriptase Inhibitors / blood
  • Reverse Transcriptase Inhibitors / pharmacokinetics*
  • Travel
  • Viral Load

Substances

  • Anti-HIV Agents
  • Antimalarials
  • Protease Inhibitors
  • Reverse Transcriptase Inhibitors
  • Doxycycline