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

Swaminathan, Soumya and Ramachandran, Geetha and Hemanth Kumar, A K and Mahalingam, Vasantha and Soundararajan, Lakshmi and Kannabiran, Bhavani P and Navaneethapandian, Poorna Ganga Devi and shah, I and Karunaianandham, R and Sikhamani, S (2011) Factors influencing plasma nevirapine levels: a study in HIV-infected children on generic antiretroviral treatment in India. Journal of Antimicrobial Chemotherapy, 66 (6). pp. 1354-1359. ISSN Print: 0305-7453 | Electronic: 1460-2091

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Abstract

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.

Affiliation:	ICMR-National Institute for Research in Tuberculosis
Item Type:	Article
Uncontrolled Keywords:	nutritional status, CYP2B6 516G.T polymorphism, pharmacokinetics
Subjects:	Tuberculosis > Clinical Research
Divisions:	Clinical Research
Depositing User:	Dr. Rathinasabapati R
Date Deposited:	17 Jun 2022 09:29
Last Modified:	17 Jun 2022 09:29
URI:	http://eprints.nirt.res.in/id/eprint/1094

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