Factors Associated with Altered Pharmacokinetics in Substance Users and Non‐Substance Users Receiving Lopinavir and Atazanavir

Abstract

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.

The association between cigarette smoking, virologic suppression, and CD4+ lymphocyte count in HIV-Infected Russian women

“…While there were no differences between infrequent and regular smokers on VL status, moderate/heavy smoking was associated with a greater likelihood of having a detectable VL. This finding may reflect the effect of smoking on metabolic enzyme activity that cause interactions with ARVs, which may reduce plasma concentrations of certain ARV classes (e.g., protease inhibitors; Higgins et al, 2007) and adversely affect virologic suppression. However, there were no differences on CD4 by smoking frequency or quantity.…”

“…This may be due, in part, to smoking’s direct, negative biological effects on the efficacy of specific antiretroviral (ARV) medications (Feldman et al, 2009; Higgins et al, 2007; Miguez-Burbano et al, 2003). Smoking may increase PLHIV’s susceptibility to opportunistic infections (e.g., pulmonary infections; Miguez-Burbano et al, 2003; Ompad et al, 2014).…”

Efflux transporters- and cytochrome P-450-mediated interactions between drugs of abuse and antiretrovirals

“…Mean trough plasma concentrations of lopinavir and atazanavir were substantially reduced in drug abuser HIV subjects relative to non abuser group (Higgins et al, 2007). A detailed review of opiate interactions with other agents has been published by Armstrong and Cozza (2003a,b).…”

Atazanavir: its role in HIV treatment

“…The therapeutic range of atazanavir lies between 150 and 850 ng/ml [21,102]; however, plasma levels in the absence of RTV have been reported to be frequently lower than the target C min of 150 ng/ml in both patients [20,25] and substance [22]. The wide interpersonal variability in atazanavir exposure has been considered an indication for twice daily dosing or therapeutic drug monitoring [23].…”