Nevirapine clearance from plasma in African adults stopping therapy: a pharmacokinetic substudy.
OBJECTIVE
To measure nevirapine elimination in African adults undertaking a structured treatment interruption (STI) in the DART trial.


METHODS
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.


CONCLUSIONS
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.
Kikaire
Ben
B
MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda.
Khoo
Saye
S
Walker
A Sarah
AS
Ssali
Francis
F
Munderi
Paula
P
Namale
Letitia
L
Reid
Andrew
A
Gibb
Diana M
DM
Mugyenyi
Peter
P
Grosskurth
Heiner
H
D000328:Adult; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy / Q000453:epidemiology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018119:Stavudine / Q000627:therapeutic use; D014454:Uganda / Q000453:epidemiology; D015215:Zidovudine / Q000627:therapeutic use; D015030:Zimbabwe / Q000453:epidemiology
D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019829:Nevirapine; D018119:Stavudine