Table 1 Case detail summary

CNS Adverse Event

Generalised tonic-clonic seizures Aggressive behavior

Acute progressive ataxia, with cerebellar signs Anti-social behavior

Generalised tonic-clonic seizures Progressively poor school performance

Absence seizures

Event Described

Generalised tonic-clonic seizure

Cerebellar dysfunction

Generalised tonic-clonic seizure

Absence seizure

Sex

Male

Female

Female

Female

Starting ART Regimen

LPV/r, 3TC, d4T

LPV/r, 3TC, d4T

LPV/r, 3TC, d4T

RTV, 3TC, d4T

Age at ART start (months)

4.9

2.4

16.7

4

ART regimen at first event

EFV, 3TC, ABC

EFV, 3TC, ABC

EFV, 3TC, ABC

EFV, 3TC, d4T

Time on EFV at first event (months)

3.3

19.8

13.7

0.9

Age at first event

4 years 6 months

4 years 10 months

7 years 6 months

4 years 7 months

EFV dose at first event (mg/kg/dose)

21 mg/kg/dose

21 mg/kg/dose

15 mg/kg/dose

21 mg/kg/dose

Age at second event

5 years

4 years 11 months

9 years 5 months

N/A

Time on EFV at second event (months)

9.6

21.3

37.9

N/A

Time on EFV at time of drug level (months)

10.1

23.5

49.7

1.2

EFV level mg/L (reference range)

20 mg/L (1-4 mg/L)

60.54 mg/L (Ref > 1 mg/L)

51.23 mg/L (1-4 mg/L)

19.62 mg/L (1-4 mg/L)

Time since last dose prior to levels (hours)

13 h post dose

13 h post dose

14 h post dose

15 h post dose

Genotype

Heterozygous CYP2B6 516G/T

Heterozygous CYP2B6 785A/G

Heterozygous CYP2B6 516G/T

Heterozygous CYP2B6 983 T/C

Heterozygous CYP2B6 516G/T Heterozygous CYP2B6 983 T/C

Homozygous CYP2B6 516 T/T