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

Swaminathan, S.; Ramachandran, G.; Hemanth Kumar, A.K.; Vasantha, M.; Lakshmi, S.; Bhavani, P.K.; Ganga Devi, N.P.; Shah, I.; Ramesh, K.; Rajasekaran, S.

Journal of Antimicrobial Chemotherapy; 2 011; 66; 1354-1359.

Background: Nevirapine is an important component of paediatric combination HIV therapy. Adequate drug exposure is necessary in order to achieve long-lasting viral suppression.

Objectives: 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.

Methods: 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.

Results: 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<0.05); there were no significant differences in trough concentrations between different nutritional groups. Nevirapine levels were significantly higher in children with TT compared with GG and GT CYP2B6 genotypes (P<0.01). Children =3 years had a 3.2 (95% confidence interval 1.07–9.45) times higher risk of having sub-therapeutic nevirapine concentrations.

Conclusions: Nevirapine blood concentrations are affected by many factors, most notably age =3 years; a combination of young age, stunting and CYP2B6 GG or GT genotype could potentially result in sub-therapeutic nevirapine concentrations. Dosing recommendations for children should be reviewed in the light of these findings.

Keywords: Nutritional status; CYP2B6 516G>T polymorphism; pharmacokinetics

Back to List of publications / Home