Therapeutic drug monitoring of boosted PIs in HIV-positive patients: undetectable plasma concentrations and risk of virological failure.
Therapeutic drug monitoring (TDM) of antiretroviral drugs is performed in selected HIV-positive patients. The aim of this study was to estimate the prevalence of undetectable plasma concentrations of ritonavir and boosted PIs and to evaluate the association between those and the 48 week risk of virological failure.



A TDM registry study and a retrospective follow-up study were conducted. Plasma concentrations were measured through validated methods. According to PI and ritonavir concentrations, patients were stratified as adherent, partially non-adherent or non-adherent. Virological outcome was evaluated 48 weeks afterwards.



The TDM registry study included 2468 samples collected from 723 patients (68.1% male, median age 43.5 years). Eighty-seven samples (3.5%, 74 patients) and 68 samples (2.8%, 52 patients) were in the partially non-adherent and non-adherent groups, respectively; more patients on atazanavir/ritonavir (7.9%) versus darunavir/ritonavir (2% twice daily and 1.9% once daily) and lopinavir/ritonavir (1.5%; P  <   0.001) were observed in the partially non-adherent group. Two hundred and ninety patients were included in the follow-up study (64.1% male, median age 40 years). Patients in the adherent group had a higher chance of viral control [81.9% (167/204)] versus the partially non-adherent group and the non-adherent group [71.7% (33/46) and 53.1% (17/32), respectively; P  =   0.001]. Based on multivariate analysis, baseline HIV RNA >50 copies/mL ( P  <   0.001), genotypic susceptibility score ≤2 ( P  =   0.001), lower nadir CD4 cell count ( P  =   0.003) and not being in the adherent group ( P  =   0.029) were independent predictors of HIV RNA >50 copies/mL at 48 weeks.



The measurement of PI and ritonavir plasma levels can uncover incomplete compliance with treatment; TDM may represent a useful tool for identifying patients in need of adherence-promoting interventions.
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
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Calcagno
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.|St Stephen's AIDS Trust, Chelsea and Westminster Hospital, London, UK.
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Pagani
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
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Ariaudo
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
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Arduino
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
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Carcieri
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
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A
D'Avolio
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
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Marinaro
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
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Tettoni
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
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Trentini
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
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G
Di Perri
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
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Bonora
D000328:Adult; D000069446:Atazanavir Sulfate / Q000097:blood / Q000627:therapeutic use; D000069454:Darunavir / Q000097:blood / Q000627:therapeutic use; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000097:blood* / Q000627:therapeutic use; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D061466:Lopinavir / Q000097:blood / Q000627:therapeutic use; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D012042:Registries; D012044:Regression Analysis; D012189:Retrospective Studies; D019438:Ritonavir / Q000097:blood* / Q000627:therapeutic use; D017211:Treatment Failure; D019562:Viral Load
D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D061466:Lopinavir; D000069446:Atazanavir Sulfate; D019438:Ritonavir; D000069454:Darunavir