Intracellular and plasma efavirenz concentrations in HIV-infected patients switching from successful protease inhibitor-based highly active antiretroviral therapy (HAART) to efavirenz-based HAART (SUSTIPHAR Study).
OBJECTIVE
To assess intracellular and plasma efavirenz concentrations in HIV-infected patients who switched to efavirenz-based highly active antiretroviral therapy (HAART) from successful protease inhibitor-based HAART.


METHODS
A total of 49 patients were included in this observational cohort study. At inclusion, all patients had plasma HIV-RNA levels<50 copies/mL and switched to efavirenz combined with two nucleoside reverse transcriptase inhibitors. Intracellular and plasma concentrations were measured 12 h post-dose, 1 month (M1) and 6 months (M6) after starting efavirenz. Virological success (VS) was defined as plasma HIV-RNA level<50 copies/mL within the first 12 months and remaining undetectable at the end of the follow-up.


RESULTS
VS was documented in 48 patients for at least 12 months (range 12-78 months). High inter-patient variabilities of intracellular and plasma efavirenz concentrations were observed (coefficients of variation>40%). At M1 and M6, respectively, median [Q1; Q3] intracellular efavirenz concentrations were 5300 [2830; 11 530] and 6790 [3870; 8790] ng/mL, median plasma efavirenz concentrations were 2050 [1600; 3100] and 2100 [1410; 2500] ng/mL. No correlation was found between intracellular and plasma concentrations. Plasma efavirenz levels exceeded the proposed threshold of 1000 ng/mL in 96% of patients from M1.


CONCLUSIONS
For moderately pre-treated HIV-infected patients with few mutations who switched to efavirenz from previous successful HAART, the proposed plasma efficacy-threshold was reached without any dosage adaptation. VS was maintained beyond 12 months, despite high inter-patient and intra-patient variabilities of intracellular and plasma efavirenz concentrations.
Djabarouti
Sarah
S
Department of Clinical Pharmacokinetics EA525, Victor Segalen Bordeaux 2, University Bordeaux, and Pharmacy Haut-Lévêque Hospital, CHU Bordeaux, Pessac, France.
Breilh
Dominique
D
Pellegrin
Isabelle
I
Lavit
Michel
M
Camou
Fabrice
F
Caubet
Olivier
O
Fleury
Hervé
H
Saux
Marie-Claude
MC
Pellegrin
Jean-Luc
JL
D000328:Adult; D000480:Alkynes; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D048588:Benzoxazines; D015331:Cohort Studies; D003521:Cyclopropanes; D005260:Female; D006678:HIV / Q000235:genetics / Q000302:isolation & purification*; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010078:Oxazines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D017320:HIV Protease Inhibitors; D010078:Oxazines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; C098320:efavirenz