Factors influencing plasma nevirapine levels: a study in HIV-infected children on generic antiretroviral treatment in India

• Published in: Journal of antimicrobial chemotherapy 2011-06, Vol.66 (6), p.1354-1359
• Main Authors: SWAMINATHAN, Soumya, RAMACHANDRAN, Geetha, KUMAR AGIBOTHU KUPPARAM, Hemanth, MAHALINGAM, Vasantha, SOUNDARARAJAN, Lakshmi, PERUMAL KANNABIRAN, Bhavani, POORANA GANGA DEVI NAVANEETHAPANDIAN, SHAH, Ira, KARUNAIANANDHAM, Ramesh, SIKHAMANI, Rajasekaran
• Format: Article
• Language: English
• Subjects: Age Factors; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - blood; Anti-HIV Agents - pharmacokinetics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral drugs; Antiretroviral Therapy, Highly Active - methods; Aryl Hydrocarbon Hydroxylases - genetics; Biological and medical sciences; Child; Child, Preschool; Children & youth; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP2B6; Drug dosages; Female; Genotype & phenotype; HIV; HIV Infections - drug therapy; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; India; Infant; Infectious diseases; Male; Medical sciences; Models, Statistical; Nevirapine - administration & dosage; Nevirapine - blood; Nevirapine - pharmacokinetics; Original Research; Oxidoreductases, N-Demethylating - genetics; Pharmacology. Drug treatments; Plasma - chemistry; Polymorphism; Polymorphism, Genetic; Regression analysis; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkr075

Nevirapine is an important component of paediatric combination HIV therapy. Adequate drug exposure is necessary in order to achieve long-lasting viral suppression. To study the influence of age, drug dose and formulation type, nutritional status and CYP2B6 516G>T polymorphism on blood concentrations of nevirapine in children treated with generic antiretroviral drugs. A multicentre study was conducted at four sites in India. HIV-infected children receiving generic nevirapine-based fixed-dose combinations were recruited. Trough and 2 h nevirapine plasma concentrations were determined by HPLC. Characterization of the CYP2B6 gene polymorphism was performed using direct sequencing. Clinical and nutritional status was recorded. Groups were compared using the Mann-Whitney U-test and multivariable logistic regression analysis was performed to identify factors contributing to low drug levels. Ninety-four children of median age 78 months were studied; 60% were undernourished or stunted. Stunted children had a significantly lower 2 h nevirapine concentration compared with non-stunted children (P