Steady-state pharmacokinetics of lopinavir/ritonavir in combination with efavirenz in human immunodeficiency virus-infected pediatric patients.

The University of Alabama at Birmingham, Birmingham, AL, USA.
The Pediatric Infectious Disease Journal (Impact Factor: 3.14). 01/2009; 28(2):159-61. DOI: 10.1097/INF.0b013e3181861d8b
Source: PubMed

ABSTRACT The pharmacokinetics of lopinavir/ritonavir (LPV/RTV) 300 mg/m twice daily and efavirenz (EFV) 350 mg/m once daily were evaluated in HIV-infected children. The minimum concentrations for LPV contained values above the target range, and the estimated minimum concentrations for EFV contained values below the range. Our data support the current LPV/RTV dose, but EFV 350 mg/m may not be sufficient.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Antiretroviral (ARV) therapy has been shown to achieve high therapeutic efficacy in treating pediatric HIV disease. The delivery of affordable, child friendly, and easy to store and administer ARV drugs is key to the successful management of HIV in children. In recent years, significant progress has been made in scaling up the access to pediatric ARV therapy among children worldwide. Despite the improved ARV drug access, multiple challenges remain concerning palatability and efficient delivery of ARV drugs to children from infancy into adolescence. Data are limited regarding developmental changes in pharmacokinetics of individual ARV drugs, and pediatric and adult fixed-dose combinations. This review provides a practical discussion regarding the pharmacokinetics of ARV agents in pediatric HIV-infected patients, as well as the practical challenges of currently available formulations, such as palatability of liquid formulations, challenges of crushing tablets, and using adult and pediatric fixed-dose combinations.
    Paediatric Drugs 06/2011; 13(3):175-92. · 1.72 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: No formal comparison has been made between the pediatric post-highly active antiretroviral therapy (HAART) outcomes of resource-limited and developed countries. To systematically quantify and compare major baseline characteristics and clinical end points after HAART between resource-limited and developed settings. Published articles and abstracts (International AIDS Society 2009, Conference on Retroviruses and Opportunistic Infections 2010) were examined from inception (first available publication for each search engine) to March 2010. Publications that contained data on post-HAART mortality, weight-for-age z score (WAZ), CD4 count, or viral load (VL) changes in pediatric populations were reviewed. Selected studies met the following criteria: (1) patients were younger than 21 years; (2) HAART was given (≥ 3 antiretroviral medications); and (3) there were >20 patients. Data were extracted for baseline age, CD4 count, VL, WAZ, and mortality, CD4 and virologic suppression over time. Studies were categorized as having been performed in a resource-limited country (RLC) or developed country (DC) on the basis of the United Nations designation. Mean percentage of deaths per cohort and deaths per 100 child-years, baseline CD4 count, VL, WAZ, and age were calculated for RLCs and DCs and compared by using independent samples t tests. Forty RLC and 28 DC publications were selected (N = 17 875 RLCs; N = 1835 DC). Mean percentage of deaths per cohort and mean deaths per 100 child-years after HAART were significantly higher in RLCs than DCs (7.6 vs 1.6, P < .001, and 8.0 vs 0.9, P < .001, respectively). Mean baseline CD4% was 12% in RLCs and 23% in DCs (P = .01). Mean baseline VLs were 5.5 vs 4.7 log(10) copies per mL in RLCs versus DCs (P < .001). Baseline CD4% and VL differ markedly between DCs and RLCs, as does mortality after pediatric HAART. Earlier diagnosis and treatment of pediatric HIV in RLCs would be expected to result in better HAART outcomes.
    PEDIATRICS 02/2011; 127(2):e423-41. · 5.30 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: There are over 2.1 million HIV-infected children worldwide, who are increasingly exposed to antiretroviral therapy. Given the enormous physiological changes associated with maturation, the role of individualized therapy and optimal dosing in children and adolescents is likely different than in adults. This review summarizes the pharmacodynamics, pharmacokinetics and pharmacogenomics of antiretroviral therapy in children and adolescents, and it discusses the roles of these in the optimization of therapy through the practice of therapeutic drug monitoring/management. Within the pharmacodynamics section are tables and discussion about what is known of the relationships between drug concentrations, inhibitory quotients and effects - both desired and toxic. The pharmacokinetics section summarizes all reported antiretroviral pharmacokinetic data in children, divided into data from population and non-population analytic approaches. Measures of interindividual pharmacokinetic variability are reported. Sampling strategies for the measurement and the interpretation of plasma antiretroviral drug concentrations are suggested, as well as dosing with degrees of renal or hepatic failure. Relevant pharmacogenomic polymorphisms are summarized, and the role for pharmacogenomics testing is discussed. Incorporation of dose adjustment on the basis of measured serum drug concentrations is reviewed, including all such paediatric experience reported in the literature. Discussion of the influences of malnutrition and herbal remedies is also included. Finally, consideration is given to future work in this field.
    Clinical Pharmacokinetics 03/2011; 50(3):143-89. · 5.49 Impact Factor


Available from