TY - JOUR
T1 - Therapeutic drug monitoring of protease inhibitors and efavirenz in HIV-infected individuals with active substance-related disorders
AU - Ma, Qing
AU - Zingman, Barry S.
AU - Luque, Amneris E.
AU - Fischl, Margaret A.
AU - Gripshover, Barbara M.
AU - Venuto, Charles S.
AU - DiFrancesco, Robin
AU - Forrest, Alan
AU - Morse, Gene D.
PY - 2011/6
Y1 - 2011/6
N2 - Background: Achieving targeted antiretroviral (ARV) plasma concentrations during long-term treatment in human immunodeficiency virus (HIV)-infected patients with substance-related disorders (SRDs) may be challenging due to a number of factors, including medication adherence, coinfection with hepatitis B or C virus, medication intolerance, and drug interactions. One approach to investigate these factors is to conduct therapeutic drug monitoring to measure ARVexposure during treatment. The objective of this study was to utilize therapeutic drug monitoring to compare efavirenz (EFV) and protease inhibitor pharmacokinetics in patients with and without SRDs. Methods: This was a multicenter, cross-sectional open-label study in patients with HIV-1 infection receiving antiretroviral therapy (ART), with active (n = 129) or without (n = 146) SRD according to National Institute on Drug Abuse criteria. Two hundred seventy-five subjects who were receiving either protease inhibitor-based or EFVbased ART regimens for .6 months were enrolled at 4 HIV treatment centers with an equal distribution of SRD and non-SRD at each site. The patients were instructed during enrollment visits with regard to the importance of adherence before and after study visits. Demographics and routine clinical laboratory tests were recorded. Results: Among the 275 patients, 47% had SRD with at least 1 substance. There were no significant differences between SRD and non-SRD groups for race, gender, age, or CD4 count at entry. A significantly higher proportion of patients with SRD had an entry HIV RNA plasma concentration .75 copies per milliliter compared with patients without SRD (40% vs 28%, P = 0.044). Logistic regression modeling revealed an association between HIV RNA plasma concentration and African American race (P = 0.017). A significantly higher proportion of SRDs also had an EFV or protease inhibitor trough concentration below the desired range (23% vs 9%, P = 0.048). Significantly lower trough concentrations were noted in patients with SRDs receiving atazanavir (0.290 vs 0.976 mg/mL) or lopinavir (3.75 vs 5.30 mg/mL). Conclusions: The pharmacokinetic data indicate differences between HIV-infected patients with and without SRDs that may influence viral load suppression during long-term ART. These findings require additional investigation in a randomized design with more intensive pharmacokinetic assessment to identify individual factors that are contributing to suboptimal ARV exposure in patients with SRDs.
AB - Background: Achieving targeted antiretroviral (ARV) plasma concentrations during long-term treatment in human immunodeficiency virus (HIV)-infected patients with substance-related disorders (SRDs) may be challenging due to a number of factors, including medication adherence, coinfection with hepatitis B or C virus, medication intolerance, and drug interactions. One approach to investigate these factors is to conduct therapeutic drug monitoring to measure ARVexposure during treatment. The objective of this study was to utilize therapeutic drug monitoring to compare efavirenz (EFV) and protease inhibitor pharmacokinetics in patients with and without SRDs. Methods: This was a multicenter, cross-sectional open-label study in patients with HIV-1 infection receiving antiretroviral therapy (ART), with active (n = 129) or without (n = 146) SRD according to National Institute on Drug Abuse criteria. Two hundred seventy-five subjects who were receiving either protease inhibitor-based or EFVbased ART regimens for .6 months were enrolled at 4 HIV treatment centers with an equal distribution of SRD and non-SRD at each site. The patients were instructed during enrollment visits with regard to the importance of adherence before and after study visits. Demographics and routine clinical laboratory tests were recorded. Results: Among the 275 patients, 47% had SRD with at least 1 substance. There were no significant differences between SRD and non-SRD groups for race, gender, age, or CD4 count at entry. A significantly higher proportion of patients with SRD had an entry HIV RNA plasma concentration .75 copies per milliliter compared with patients without SRD (40% vs 28%, P = 0.044). Logistic regression modeling revealed an association between HIV RNA plasma concentration and African American race (P = 0.017). A significantly higher proportion of SRDs also had an EFV or protease inhibitor trough concentration below the desired range (23% vs 9%, P = 0.048). Significantly lower trough concentrations were noted in patients with SRDs receiving atazanavir (0.290 vs 0.976 mg/mL) or lopinavir (3.75 vs 5.30 mg/mL). Conclusions: The pharmacokinetic data indicate differences between HIV-infected patients with and without SRDs that may influence viral load suppression during long-term ART. These findings require additional investigation in a randomized design with more intensive pharmacokinetic assessment to identify individual factors that are contributing to suboptimal ARV exposure in patients with SRDs.
KW - Antiretroviral therapy
KW - Substance-related disorders
KW - Therapeutic drug monitoring
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U2 - 10.1097/FTD.0b013e31821d3adb
DO - 10.1097/FTD.0b013e31821d3adb
M3 - Article
C2 - 21544014
AN - SCOPUS:80051793349
SN - 0163-4356
VL - 33
SP - 309
EP - 314
JO - Therapeutic Drug Monitoring
JF - Therapeutic Drug Monitoring
IS - 3
ER -