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Nevirapine clearance from plasma in African adults stopping therapy: a pharmacokinetic substudy

Kikaire, Bena; Khoo, Sayec; Walker, A Sarahd; Ssali, Francisb; Munderi, Paulaa; Namale, Letitiab; Reid, Andrewe; Gibb, Diana Md; Mugyenyi, Peterb; Grosskurth, Heinera; on behalf of the DART Trial Team

doi: 10.1097/QAD.0b013e3280121801
Clinical Science

Objective: To measure nevirapine elimination in African adults undertaking a structured treatment interruption (STI) in the DART trial.

Design: Cohort (16 women, 5 men; median weight 61 kg) within a randomized trial of management strategies.

Methods: Plasma nevirapine was measured by validated high performance liquid chromatography at 0,1,2,3 and 4 weeks after stopping the drug in a subset of patients undertaking an STI. All patients continued lamivudine plus zidovudine/stavudine for a further 7 days.

Results: Two patients with no or low plasma nevirapine concentration at baseline were excluded. Geometric mean plasma concentration when nevirapine was stopped in the remaining 19 patients was 6421 ng/ml (range, 3724–9473). Nevirapine was detected in 15/18 (83%) patients at 1 week, and 5/19 (26%) patients at 2 weeks but was not found any samples collected after 2 weeks. Only one patient had > 100 ng/ml (limit of quantification) at 2 weeks (415 ng/ml, female). The median times to reach thresholds of 200, 100 and 20 ng/ml (limit of detection) were estimated to be 7.6 [interquartile range (IQR), 7.0–10.1], 9.3 (IQR, 8.7–13.0) and 13.2 (IQR, 12.3–18.4) days, respectively, with 3/19 (16%) and 14/19 (74%) estimated to have reached < 20 ng/ml by 7 and 14 days, respectively.

Conclusion: Although elimination of nevirapine was faster than previously published after a single dose, the data suggest that an additional staggered period of 7–10 days with dual nucleotide reverse transcriptase inhibitor cover is necessary for African patients discontinuing nevirapine.

From the aMRC/UVRI Uganda Research Unit on AIDS, Entebbe

bJoint Clinical Research Centre, Kampala, Uganda

cUniversity of Liverpool, Liverpool, UK

dMRC Clinical Trials Unit, London, UK

eUniversity of Zimbabwe, Harare, Zimbabwe.

Received 7 September, 2006

Accepted 16 October, 2006

Correspondence to Dr A.S. Walker, MRC Clinical Trials Unit, 222 Euston Rd, London, NW1 2DA, UK. E-mail: s.walker@ctu.mrc.ac.uk

© 2007 Lippincott Williams & Wilkins, Inc.