title: Lack of effect of doxycycline on trough concentrations of protease inhibitors or non-nucleoside reverse transcriptase inhibitors in HIV-infected patients.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: Service de maladies infectieuses et tropicales, Hôpital Avicenne-APHP, Bobigny, France.
authors: S
authors: S
authors: Abgrall
authors: INSERM, UMR-S 738, Paris, F-75018 France Université Paris Diderot, Sorbonne Paris Cité, UMR-S 738, Paris, F-75018 France.
authors: J
authors: J
authors: Le Bel
authors: Service de maladies infectieuses et tropicales, Hôpital Avicenne-APHP, Bobigny, France.
authors: N
authors: N
authors: Lele
authors: INSERM, UMR-S 738, Paris, F-75018 France Université Paris Diderot, Sorbonne Paris Cité, UMR-S 738, Paris, F-75018 France Service de Biostatistique, AP-HP, Hôpital Bichat, Paris, F-75018 France.
authors: C
authors: C
authors: Laouénan
authors: Department of Clinical Pharmacokinetics, AP-HP, Bichat-Claude Bernard Hospital and EA449 Université Paris 7, Paris, F-75018 France.
authors: N
authors: N
authors: Eychenne
authors: INSERM, UMR-S 738, Paris, F-75018 France Université Paris Diderot, Sorbonne Paris Cité, UMR-S 738, Paris, F-75018 France Service de Biostatistique, AP-HP, Hôpital Bichat, Paris, F-75018 France.
authors: F
authors: F
authors: Mentré
authors: Department of Clinical Pharmacokinetics, AP-HP, Bichat-Claude Bernard Hospital and EA449 Université Paris 7, Paris, F-75018 France.
authors: G
authors: G
authors: Peytavin
authors: Service de maladies infectieuses et tropicales, Hôpital Avicenne-APHP, Bobigny, France Université Paris 13, Bobigny, France.
authors: O
authors: O
authors: Bouchaud
mesh_terms: D019380:Anti-HIV Agents / Q000097:blood / Q000493:pharmacokinetics*; D000962:Antimalarials / Q000493:pharmacokinetics*; D004318:Doxycycline / Q000493:pharmacokinetics*; D004347:Drug Interactions; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D008288:Malaria / Q000517:prevention & control; D011480:Protease Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D018894:Reverse Transcriptase Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D014195:Travel; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D000962:Antimalarials; D011480:Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D004318:Doxycycline
keywords: antiretroviral drug; cohort; doxycycline; interaction; malarial drug; pharmacokinetic