A pharmacogenomic prospective randomized controlled trial of CYP2B6 polymorphisms and efavirenz dose adjustment among HIV-infected Thai patients: a pilot study

Figures & data

Figure 1 Study flow diagram.

Abbreviations: ART, antiretroviral therapy; CYP2B6, cytochrome P450 2B6.

Table 1 Baseline characteristics of 24 HIV-infected patients

Characteristics	CYP2B6-guided group (N=12)	Control group (N=12)
Men, n (%)	10 (83.3)	6 (50.0)
Median (IQR) age, years	36.5 (26.5–44.3)	38.5 (23.8–50.5)
Median (IQR) body mass index, kg/m^2	22.0 (20.9–24.5)	20.5 (16.0–22.4)
Route of HIV acquisition, n (%)
Heterosexual contact	5 (41.7)	6 (50.0)
Homosexual contact	6 (50.0)	3 (25.0)
Injecting drug user	1 (8.3)	3 (25.0)
CDC category, n (%)
A	9 (75.0)	8 (66.7)
B	1 (8.3)	1 (8.3)
C	2 (16.7)	3 (25.0)
Median (IQR) plasma	4.63 (4.45–5.47)	4.82 (3.94–5.65)
HIV RNA, log10 copies/mLa
Median (IQR) CD4 cell count, cells/mL	223 (53–326)	274 (101–314)
Positive HBsAg, n (%)	2 (16.7)	1 (8.3)
Positive anti-HCV, n (%)	1 (8.3)	0
Median (IQR) alanine aminotransferase, U/L	39.5 (27.3–71.5)	30.5 (23.0–43.0)
Median (IQR) creatinine, mg/dL	0.94 (0.85–1.05)	0.83 (0.69–0.92)

Notes:

a Plasma HIV RNA was performed in six patients in the CYP2B6-guided group and in seven patients in the control group.

Abbreviations: CYP2B6, cytochrome P450 2B6; SD, standard deviation; IQR, interquartile range; HbsAg, surface antigen of the hepatitis B virus; HCV, hepatitis C virus; CDC, Center for Disease Control and Prevention.

Table 2 Polymorphism CYP2B6 in 24 HIV-infected patients

Polymorphism in CYP2B6, n (%)	CYP2B6-guided group (N=12)	Control group (N=12)
*1/*1	3 (25.0)	6 (50.0)
*1/*2	0	1 (8.3)
*1/*4	2 (16.7)	0
*1/*6	6 (50.0)	3 (25.0)
*4/*6	0	1 (8.3)
*6/*6	1 (8.3)	1 (8.3)

Notes: CYP2B6 haplotype determination was interpreted using the Human Cytochrome P450 (CYP) Allele Nomenclature Database (http://www.cypalleles.ki.se/cyp2b6.htm). All SNPs were included for CYP2B6 haplotype interpretation.

Abbreviations: CYP2B6, cytochrome P450 2B6; SNP, single nucleotide polymorphism.

Figure 2 Efavirenz concentrations in plasma at 4, 12, and 24 weeks.

Note: The boxes represent interquartile range and lines represent minimum and maximum value.
Abbreviation: CYP2B6, cytochrome P450 2B6.

Table 3 Primary and secondary outcomes in 17 HIV-infected patients

Outcomes	CYP2B6-guided group (N=9)	Control group (N=8)	P-value
Primary outcome, n (%)
HIV RNA <40 copies/mL at week 24	9 (100)	8 (100)	1.000
Secondary outcome
Mean (SD) efavirenz level, µg/mL
Week 4	1.449 (0.904)	1.900 (1.013)	0.824
Week 12	1.361 (0.447)	1.542 (1.024)	0.254
Week 24	1.890 (0.761)	1.823 (0.845)	0.837
Adverse events, n (%)a
Overall	11 (91.7)	11 (91.7)
Neuropsychiatric events
Dizziness	8 (66.7)	10 (83.3)
Scary dream	0	1 (8.3)
Vivid dream	2(16.7)	0
Difficult to concentration	1 (8.3)	0
Confusion	1 (8.3)	0
Nausea	2 (16.7)	1 (8.3)
Vomiting	2 (16.7)	1 (8.3)
Rash	2 (16.7)	1 (8.3)
Hepatitisb	1 (8.3)	0

Notes:

a A dverse events might occur (more than one event in some patients);

b elevation of alanine aminotransferase more than three times the normal upper limit.

Abbreviations: CYP2B6, cytochrome P450 2B6; SD, standard deviation.