Pharmacokinetics of abacavir and lamivudine in infants living with HIV with and without rifampicin co-treatment.

BACKGROUND

Lamivudine and abacavir are key components of first-line paediatric antiretroviral therapy (ART). Rifampicin is part of drug-sensitive TB treatment in children. Rifampicin induces UDP-glucuronosyltransferases and renal transporters and inhibits gastrointestinal transporters involved in the pharmacokinetics of abacavir and lamivudine, but pharmacokinetic data on this potential interaction in infants are scarce.

OBJECTIVE

To evaluate the effect of rifampicin on the pharmacokinetics of abacavir and lamivudine in infants aged 28-365 days and weighing >3 kg.

METHODS

This pharmacokinetic sub-study was nested within the EMPIRICAL trial (NCT03915366). Eighteen infants from Mozambique, Uganda, Zambia and Zimbabwe received once-daily fixed-dose abacavir/lamivudine with dolutegravir according to WHO guidelines. Five infants received ART alone and 13 received ART plus rifampicin-based tuberculosis treatment. Abacavir/lamivudine dosing was unchanged during rifampicin co-treatment. Six plasma concentrations were measured over 24 h and analysed using non-compartmental pharmacokinetic analysis.

RESULTS

Median (IQR) age and weight were 6.8 (5.2-10.2) months and 6.0 (5.3-6.8) kg, respectively, and were comparable between groups. Abacavir exposure was comparable with and without rifampicin (AUC0-24h: 21.9 versus 21.0 h mg/L; Cmax: 6.2 versus 6.3 mg/L, respectively). Lamivudine exposure was also comparable (AUC0-24h: 12.6 versus 12.4 h mg/LL, respectively). The slightly higher Cmax (2.4 versus 1.9 mg/L) in the rifampicin group is probably due to interindividual variability or increased absorption from rifampicin's inhibition of gastrointestinal drug transporters, and considered not clinically relevant.

CONCLUSIONS

Rifampicin co-treatment had minimal impact on abacavir and lamivudine pharmacokinetics in infants. Dose adjustment of abacavir/lamivudine is not required during rifampicin-containing tuberculosis treatment.