Factors associated with altered pharmacokinetics in substance users and non-substance users receiving lopinavir and atazanavir.
Substance use is highly prevalent in HIV-infected individuals in the United States, and clinical management is complicated by the need for antiretroviral treatment, addiction therapy, variable medication adherence, and co-morbidities. The interrelation between HIV and substance use prompted our investigation to examine substance use and self-reported medication adherence in patients receiving the HIV-1 protease inhibitors, atazanavir (ATV) or lopinavir (LPV). ATV and LPV pharmacokinetics were determined by measuring plasma concentrations in subjects with active substance use (SU group) or with no active substance use (NSU group). No difference in adherence was observed between groups (p > 0.05). The mean SU ATV trough was 0.550+/-0.45 microg/mL; the mean NSU ATV trough was 0.780+/-0.590 microg/mL (p > 0.05). The mean SU LPV trough was 4.02+/-2.39 microg/mL; the mean NSU LPV trough was 6.67+/-0.910 microg/mL (p = 0.01). Co-factors found to be associated with variation in ATV and LPV concentrations included concurrent methadone use, cigarette smoking, and substance use status. These data indicate that chronic HIV treatment may be assisted with plasma concentration monitoring to identify those patients who may require dosage modification and/or regimen adjustment in order to optimize antiretroviral effects.
Higgins
Niamh
N
Pharmacotherapy Research Center, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Amherst, New York 14260, USA.
Zingman
Barry S
BS
Slish
Judianne
J
Reichman
Richard C
RC
Fischl
Margaret A
MA
Gripshover
Barbara
B
Tooley
Kelly
K
Boston
Naomi
N
Forrest
Alan
A
Brazeau
Dan
D
Catanzaro
Linda M
LM
DiFrancesco
Robin
R
Lliguicota
Francesco
F
Ma
Qing
Q
Morse
Gene D
GD
D000328:Adult; D019380:Anti-HIV Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D000069446:Atazanavir Sulfate; D018791:CD4 Lymphocyte Count; D015897:Comorbidity; D016903:Drug Monitoring; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D061466:Lopinavir; D008297:Male; D008691:Methadone / Q000627:therapeutic use; D008875:Middle Aged; D009842:Oligopeptides / Q000493:pharmacokinetics*; D010349:Patient Compliance; D011725:Pyridines / Q000493:pharmacokinetics*; D011744:Pyrimidinones / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012907:Smoking / Q000453:epidemiology; D019966:Substance-Related Disorders / Q000097:blood / Q000453:epidemiology / Q000378:metabolism*
D019380:Anti-HIV Agents; D009842:Oligopeptides; D011725:Pyridines; D011744:Pyrimidinones; D061466:Lopinavir; D000069446:Atazanavir Sulfate; D008691:Methadone