Therapeutic drug monitoring of antiretrovirals for people with HIV

Kredo, Tamara; Walt, Jan-Stefan van der; Siegfried, Nandi; Cohen, Karen; Sinxadi, Phumla

doi:10.1002/14651858.cd007268

Cited by 30 publications

(34 citation statements)

References 20 publications

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“…To ameliorate patient management, the determination of anti-HIV drug plasma levels on a routine basis (i.e., therapeutic drug monitoring; TDM) could represent a useful clinical tool, enabling the study of the relationship between drug plasma levels, drug toxicity, virological response failure, and treatment fine-tuning (3)(4)(5). However, although TDM has been incorporated into anti-HIV treatment guidelines (3,4,(6)(7)(8), prospective randomized clinical trials assessing the usefulness of this strategy have shown contradictory results (3,9).…”

Section: Introductionmentioning

confidence: 99%

Simultaneous determination of lamivudine, lopinavir, ritonavir, and zidovudine concentration in plasma of HIV‐infected patients by HPLC‐MS/MS

Notari¹,

Sergi²,

Montesano³

et al. 2012

IUBMB Life

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SummaryThe nucleoside reverse transcriptase inhibitors lamivudine and zidovudine and the protease inhibitors lopinavir and ritonavir are currently used in anti-human immunodeficiency virus (HIV) therapy. Here, a high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method, using a hybrid quadrupole time-of-flight mass analyzer, is reported for the simultaneous quantification of lamivudine, lopinavir, ritonavir, and zidovudine in plasma of HIV-infected patients. The volume of plasma sample was 600 lL. Plasma samples were extracted by solid-phase using 1 cc Oasis HLB Cartridge (divinylbenzene and N-vinylpyrrolidone) and evaporated in a water bath under nitrogen stream. The extracted samples were reconstituted with 100-lL methanol. Five microliters of the reconstituted samples were injected into a HPLC-MS/MS apparatus, and the analytes were eluted on a Vydac column (250 3 1.0 mm i.d.) filled with 3-lm C 18 particles. The mobile phase was delivered at 70 lL/ min with a linear gradient elution, both acetonitrile and ultrapure water solvents contained 0.2% formic acid. The calibration curves were linear from 0.47 to 20 ng/mL. The absolute recovery ranged between 91 and 107%. The minimal concentration of lamivudine, lopinavir, ritonavir, and zidovudine detectable by HPLC-MS/MS is 0.47, 0.28, 0.30, and 0.66 ng/mL, respectively. The great advantage of the new HPLC-MS/MS method here reported is the possibility to achieve a very high specificity toward the selected anti-HIV drugs, despite the simple and rapid sample preparation. Moreover, this method is easily extendible to the analysis of co-administrated drugs. Abbreviations AIDS, acquired immune deficiency syndrome; HAART, highly active anti-retroviral therapy; HIV, human immunodeficiency virus; HPLC-MS/MS, high-performance liquid chromatography-mass spectrometry; LOD, limit of detection; LOQ, limit of quantification; NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; QqTOF, quadrupole time-of-flight; SPE, solid-phase extraction; TDM, therapeutic drug monitoring; TOF, time-of-flight.

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Section: Introductionmentioning

confidence: 99%

Simultaneous determination of lamivudine, lopinavir, ritonavir, and zidovudine concentration in plasma of HIV‐infected patients by HPLC‐MS/MS

Notari¹,

Sergi²,

Montesano³

et al. 2012

IUBMB Life

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“…Although a concentration-effect relationship has been suggested for intracellular NRTI concentrations and antiretroviral efficacy, NRTIs are generally poor candidates for therapeutic drug monitoring due to the complexity of [19,20]. Drug plasma concentrations may not reflect intracellular concentrations, making it difficult to directly correlate plasma concentrations with therapeutic efficacy.…”

Section: Discussionmentioning

confidence: 99%

Dosing Nucleoside Reverse Transcriptase Inhibitors in Adults Receiving Continuous Veno-Venous Hemofiltration

et al. 2015

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“…Discordant data were reported in those trials: no improved virological response to HAART in subjects whose doses were adjusted was observed in 5 RTCs [15][16][17][18][19], and virological benefit was reported in two of them [20,21]. A recent Cochrane review on the use of TDM during HAART did not support the routine use of TDM in clinical practice, but it suggested that specific clinical indications such as pregnancy can be studied to confirm its role in improving virological outcomes [22].…”

Section: Discussionmentioning

confidence: 99%

Antiretroviral Therapeutic Drug Monitoring in HIV-Infected Pregnant Women: Maternal Immunovirological Outcome at Delivery and During the 18 Month Follow-Up Period

Nicastri

Ivanović

Signore

et al. 2012

CHR

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No data are available on the long-term immunovirological outcome of HIV-positive pregnant women experiencing sub-therapeutic antiretroviral drug (ARV) concentrations during pregnancy. The objective of our study was to assess the long-term virological outcome in pregnant women treated with HAART. A prospective, multi-center study enrolled 60 HIV-infected pregnant women stratified into 3 groups according to the response to HAART. Group A, women successfully treated with HAART; Group B, women with confirmed virological failure during HAART; Group C, women successfully treated with HAART during pregnancy for prevention of vertical transmission only. Smoking, alcohol use, low adherence to therapy, and increased viral load at delivery were significantly associated to virological failure at univariate analysis. At multivariate regression analysis, only adherence to therapy was reported as an independent variable related to the virological response (p < 0.001). Virological failure during follow-up was reported in 2 (25.0%) of the 8 women with sub therapeutic Ctrough and in 4 of the 33 (12.1%) women with therapeutic Ctrough (p=0.33). In group C, the viro-immunological set points during follow-up did not differ from those observed before HAART initiation. No significantly increased rate of virological failure after delivery was reported in women with sub-therapeutic ARV concentrations during pregnancy and long-term follow-up. The long-term virological outcome was independently associated to reduced adherence to therapy. Evaluation of the clinical impact of the low plasma ARV concentrations during pregnancy on the long-term virological outcome deserves further larger studies.

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Therapeutic drug monitoring of antiretrovirals for people with HIV

Cited by 30 publications

References 20 publications

Simultaneous determination of lamivudine, lopinavir, ritonavir, and zidovudine concentration in plasma of HIV‐infected patients by HPLC‐MS/MS

Simultaneous determination of lamivudine, lopinavir, ritonavir, and zidovudine concentration in plasma of HIV‐infected patients by HPLC‐MS/MS

Dosing Nucleoside Reverse Transcriptase Inhibitors in Adults Receiving Continuous Veno-Venous Hemofiltration

Antiretroviral Therapeutic Drug Monitoring in HIV-Infected Pregnant Women: Maternal Immunovirological Outcome at Delivery and During the 18 Month Follow-Up Period

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