Open AccessPrevalence of Multiple Dideoxynucleoside Analogue Resistance (MddNR) in a Multicenter Cohort of HIV-1–Infected Italian Patients With Virologic Failure
Author(s) -
Claudia Balotta,
Michela Violin,
Laura Monno,
Patrizia Bagnarelli,
Chiara Riva,
Guido Facchi,
Alberto Berlusconi,
Monica Lippi,
Stefano Rusconi,
Massimo Clementi,
Massimo Galli,
Gioacchino Angarano,
Mauro Moroni
Publication year - 2000
Publication title -
journal of acquired immune deficiency syndromes
Language(s) - English
Resource type - Journals
eISSN - 1944-7884
pISSN - 1525-4135
DOI - 10.1097/00126334-200007010-00007
Subject(s) - didanosine , stavudine , zidovudine , virology , reverse transcriptase , nucleoside analogue , reverse transcriptase inhibitor , medicine , drug resistance , abacavir , nucleoside reverse transcriptase inhibitor , biology , lamivudine , virus , sida , nucleoside , viral load , viral disease , antiretroviral therapy , genetics , polymerase chain reaction , hepatitis b virus , gene
For opiate-dependent injection drug users infected with HIV, methadone therapy may facilitate adherence to complex highly active antiretroviral therapy (HAART) regimens. Current HAART regimens include one or more nucleoside analogues. We investigated the effects of methadone on the pharmacokinetics of the tablet formulation of didanosine (ddI) and of stavudine (d4T) in 17 study subjects on stable methadone therapy and in 10 untreated controls. Methadone treatment reduced the measured areas under the time-concentration curve (AUC0-6) by 63% for ddI (p =.04) and by 25% for d4T (p =.005) and the extrapolated AUCs for the full dosing interval (AUC0-12) by 57% for ddI (p =.11) and by 23% for d4T (p =. 02). Peak drug concentrations (Cmax) were reduced by 66% (p =.007) and 44% (p =.001) for ddI and d4T, respectively. The effects on AUC and Cmax appeared to result primarily from decreases in bioavailability. Methadone also delayed drug absorption. Trough levels for methadone did not differ significantly from those in historical controls, suggesting that ddI and d4T did not substantially alter methadone disposition. The results suggest that larger doses of the tablet formulation or an alternate formulation may be needed when didanosine is given to study subjects treated with methadone.