Relationship Between Antiretroviral Drug Plasma Concentrations and Viral Load in Children

Jm, Tréluyer; Burgard, Marianne; Cazali, N; Quartier, Pierre; Veber, Florence; E, Rey; Alkaer, G; Rouzioux, C; Pons, Gérard; Blanche, Stéphane

doi:10.1097/00126334-200301010-00016

Cited by 5 publications

(3 citation statements)

References 25 publications

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“…Our findings were not substantially altered in either analysis. The use of therapeutic drug monitoring is complicated by insufficient knowledge of the target plasma concentrations particularly in children on ART in whom the optimal drug concentrations have not been clearly defined [20]. In this study, we used reference values for plasma lopinavir concentrations derived largely from adult studies.…”

Section: Discussionmentioning

confidence: 99%

Plasma Lopinavir Concentrations Predict Virological Failure in a Cohort of South African Children Initiating a Protease-Inhibitor-Based Regimen

et al. 2013

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Background Poor adherence to antiretroviral therapy contributes to pharmacokinetic variability and is the major determinant of virological failure. However, measuring treatment adherence is difficult, especially in children. We investigated the relationship between plasma lopinavir concentrations, pretreatment characteristics and viral load >400 copies/ml. Methods A total of 237 HIV-infected children aged 4–42 months on lopinavir/ritonavir oral solution were studied prospectively and followed for up to 52 weeks. Viral load and lopinavir concentration were measured at clinic visits 12, 24, 36 and 52 weeks after starting treatment. Cox multiple failure events models were used to estimate the crude and adjusted effect of lopinavir concentrations on the hazard of viral load >400 copies/ml. Results The median (IQR) pretreatment CD4+ T-lymphocyte percentage was 18.80% (12.70–25.35) and 53% of children had a pretreatment viral load >750,000 copies/ml. The median (IQR) weight-for-age and height-for-age z-scores were −2.17 (−3.35–−2.84) and −3.34 (−4.57–−3.41), respectively. Median (IQR) lopinavir concentrations were 8.00 mg/l (4.11–12.42) at median (IQR) 3.50 h (2.67–4.25) after the dose. The hazard of viral load >400 copies/ml was increased with lopinavir concentrations <1 mg/l versus ≥1 mg/l (adjusted hazard ratio 2.3 [95% CI 1.63, 3.26]) and lower height-for-age z-scores. Conclusions Low lopinavir concentrations (<1 mg/l) are associated with viraemia in children. This measure could be used as a proxy for adherence and to determine which children are more likely to fail.

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Section: Discussionmentioning

confidence: 99%

Plasma Lopinavir Concentrations Predict Virological Failure in a Cohort of South African Children Initiating a Protease-Inhibitor-Based Regimen

et al. 2013

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“…One of the potential problems with TDM is knowing the target concentration 14 . The optimal target plasma concentrations for the therapeutic monitoring of ARV drugs have not been clearly defined for children.…”

Section: Discussionmentioning

confidence: 99%

Comparison of levels of antiretroviral drugs with efficacy in children with HIV infection

et al. 2010

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“…Adherence measured by objective drug level monitoring has been poorly documented in resource poor settings (9). Target drug concentrations of zidovudine and lamivudine have not been clearly defined and there is no consensus on recommended minimum plasma concentrations particularly in children (10). The World Health Organization has also developed simplified weight band dosing for paediatric ARV which has the potential to provide a simple and effective dosing strategy for resource limited settings (11).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Zidovudine, Lamivudine and Nevirapine Plasma Concentrations and Factors influencing their Plasma Drug Exposure in Children Aged 2–14 Years Living with HIV at the Lagos University Teaching Hospital

Nwaiwu

Akinleye

Akindele

et al. 2018

JBMS

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Background: Plasma concentrations of antiretroviral drugs have become important determinants of treatment success, treatment failure and toxicity. There is a paucity of antiretroviral plasma concentration data in our local paediatric human immunodeficiency virus (HIV) literature in Nigeria. Objective: To evaluate plasma concentrations of zidovudine, lamivudine, and nevirapine after 2 years of combination therapyand to determine factors that influence plasma drug exposure in children aged 2–14 years living with HIV. Subjects and Methods: This was a cross-sectional prospective study in which plasma concentrations of zidovudine, lamivudine and nevirapine were simultaneously determined using a simple, rapid and sensitive high performance liquid chromatographic method with UV detection. Plasma concentrations obtained were compared to published data (Cmin and Cmax ) and regulatory reference data (C max only). Results: The median plasma concentrations were 0.062, 1.435 and 4.450 μg/mL for zidovudine, lamivudine and nevirapine respectively. Supratherapeutic plasma zidovudine, lamivudine and nevirapine levels occurred in 33%, 22% and 26% of patients respectively. Supratherapeutic levels were however not significantly associated with adverse events (p>0.05).At 2 years,age (p=0.018) was significantly associated with zidovudine concentrations, with older children having higher levels. There was a perfect agreement between adherence and plasma concentrations of nevirapine (p=0.020). Conclusion: Plasma concentrations were similar to levels previously reported in children with therapeutic, supratherapeutic and nevirapine supratherapeutic levels. There were no observed significant associations between plasma drug concentrations and toxicity. The clinical relevance of observed significant higher levels of plasma zidovudine with increasing age, and supratherapeutic plasma exposures of zidovudine, lamivudine and nevirapine needs further investigations.

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Relationship Between Antiretroviral Drug Plasma Concentrations and Viral Load in Children

Cited by 5 publications

References 25 publications

Plasma Lopinavir Concentrations Predict Virological Failure in a Cohort of South African Children Initiating a Protease-Inhibitor-Based Regimen

Plasma Lopinavir Concentrations Predict Virological Failure in a Cohort of South African Children Initiating a Protease-Inhibitor-Based Regimen

Comparison of levels of antiretroviral drugs with efficacy in children with HIV infection

Evaluation of Zidovudine, Lamivudine and Nevirapine Plasma Concentrations and Factors influencing their Plasma Drug Exposure in Children Aged 2–14 Years Living with HIV at the Lagos University Teaching Hospital

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