Plasma lopinavir concentrations predict virological failure in a cohort of South African children initiating a protease-inhibitor-based regimen

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...

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Bibliographic Details
Published in:Antiviral therapy 2014-01, Vol.19 (4), p.399-406
Main Authors: Moholisa, Retsilisitsoe R, Schomaker, Michael, Kuhn, Louise, Meredith, Sandra, Wiesner, Lubbe, Coovadia, Ashraf, Strehlau, Renate, Martens, Leigh, Abrams, Elaine J, Maartens, Gary, McIlleron, Helen
Format: Article
Language:English
Subjects:
Anti-HIV Agents - pharmacokinetics
Anti-HIV Agents - therapeutic use
Antiretroviral Therapy, Highly Active
Child, Preschool
Drug Monitoring
Female
HIV Infections - drug therapy
HIV Infections - virology
HIV Protease Inhibitors - pharmacokinetics
HIV Protease Inhibitors - therapeutic use
HIV-1
Human immunodeficiency virus
Humans
Infant
Male
Retrospective Studies
Treatment Failure
Treatment Outcome
Viral Load
Viremia
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Summary: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. 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. 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
ISSN:1359-6535
2040-2058
DOI:10.3851/IMP2749