The effects of systemic efavirenz exposure, sex and age on risk of viral non-suppression

Pharmacokinetic (PK) sub study from CHAPAS-3 suggests new paediatric target minimum concentrations for efavirenz (EFV) – according to data presented at the 7th International Workshop on HIV Pediatrics.

CHAPAS-3 (Children with HIV 1 in Africa, Pharmacokinetics and Adherence/Acceptability of Simple Antiretroviral Regimens) was an open-label, randomised, phase 2/3 trial, conducted in Zambia and Uganda to evaluate new solid, dispersible, scored, antiretroviral fixed-dose combination and single drugs in African children.

The sub study was conducted to describe the effect of systematic EFV exposure on viral suppression and determine the minimum exposure predictive of reduced risk of non-suppression.

The investigators used Cox proportional hazards regression models to estimate the risk of viral non-suppression (>100 copies/mL) associated with EFV exposure and other factors as hazard ratio.

They analysed 590 matched PK/viral load samples from 118 children 1.7 to 13.5 years of age.

They found the risk of non-suppression was best described using a non-linear model that showed risk of non viral suppression decreased by 40% for every 2-fold increase in mid dose concentrations (95% CI: 24 to 51%) p<0.0001. The risk reached a plateau around values of 8mg/L (log2 C12h).

Multivariate analysis found male sex and older age to be other risk factors for viral non-suppression. See table 1.

Table 1: Multivariate analysis risk factors for non-suppression
Group	Relative hazard	95% CI	p-value
Girls <8	Reference
Boys <8	5.55	1.97 to 15.5	0.001
Girls>8	12.72	4.89 to 33. 07	<0.001
Boys>8	11.23	2.64 to 47.76	0.001

Table 1: Multivariate analysis risk factors for non-suppression

Group

Relative hazard

95% CI

p-value

Girls <8

Reference

Boys <8

5.55

1.97 to 15.5

0.001

Girls>8

12.72

4.89 to 33. 07

<0.001

Boys>8

11.23

2.64 to 47.76

0.001

The most predictive C12h cut off value for risk of viral non-suppression was 1.2mg/L, p<0.001. Based on their results the investigators suggested that mid-dose mid dose interval concentrations of 1.2 mg/L should be used as the new EFV paediatric target minimum concentrations.

Bienczak A et al. The effect of systematic exposure to efavirenz, sex and age on the risk of virological non-suppression in HIV-infected children. 7th International Workshop on HIV Pediatrics, 17-18 July, Vancouver, Canada. Oral abstract 2.
http://regist2.virology-education.com/2015/7hivped/06_.pdf