Methadone dosing strategies in HIV-infected injection drug users enrolled in a directly observed therapy program.
OBJECTIVE
We have measured methadone dose adjustments and treatment responses after nevirapine (NVP)-, efavirenz (EFV)-, ritonavir-boosted lopinavir (LPV/r), or atazanavir (ATV; with or without ritonavir)-based highly active antiretroviral therapy (HAART) was initiated in injection drug users (IDUs).


METHODS
We identified 120 IDUs receiving HAART and methadone within a directly observed therapy (DOT) program. Follow-up was according to clinical standards, with changes in methadone dose being made as required to achieve clinical stabilization within the first 3 months of HAART.


RESULTS
The observed median methadone dose changes from baseline were 20 mg/d (P<0.001) in patients on NVP, with 32 (86%) of 37 patients requiring daily dose increases, and 7.5 mg/d (P=0.004) in patients on EFV, with 11 (61%) of 18 patients requiring daily dose increases. Conversely, median changes were 0 mg/d for patients on LPV/r (P=0.56) or ATV (P=0.95). Virologic suppression (HIV RNA<400 copies/mL) was achieved in 26 (70%) of 37, 12 (67%) of 18, 25 (76%) of 33, and 24 (75%) of 32 patients receiving NVP-, EFV-, LPV/r-, and ATV-based regimens, respectively (P=0.89).


CONCLUSIONS
Although methadone-based DOT can be a successful tool for the coadministration of HAART, careful monitoring is required to ensure that methadone withdrawal does not adversely affect the goals of treatment, particularly when nonnucleoside reverse transcriptase inhibitors are used.
Tossonian
Harout K
HK
Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.
Raffa
Jesse D
JD
Grebely
Jason
J
Trotter
Brendon
B
Viljoen
Mark
M
Mead
Annabel
A
Khara
Milan
M
McLean
Mark
M
Duncan
Fiona
F
Fraser
Chris
C
DeVlaming
Stanley
S
Conway
Brian
B
D000284:Administration, Oral; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D023801:Directly Observed Therapy; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008691:Methadone / Q000008:administration & dosage / Q000627:therapeutic use*; D009294:Narcotics / Q000008:administration & dosage / Q000627:therapeutic use*; D015819:Substance Abuse, Intravenous / Q000150:complications / Q000188:drug therapy*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000209:etiology; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D009294:Narcotics; D008691:Methadone