Abacavir (ABC) is licensed for infants >3 months of age while WHO recommends use in HIV-infected children ≥4 weeks of age and ≥3 kg. ABC is metabolized in the liver via UDPGT and ADH enzymes, and information describing ABC disposition during the first few months of life is lacking. We describe ABC pharmacokinetic (PK) and safety data in HIV-infected normal and low birth weight (LBW) infants initiating ABC within the first 3 months of life.
IMPAACT P1106 is an opportunistic, multi-arm study of PK and safety in LBW infants conducted in South Africa on antiretroviral and antituberculosis medicines. Arm 5 included HIV-infected infants receiving ABC, lamivudine and lopinavir/ritonavir. Plasma samples for ABC PK assessment were collected pre-dose (C0), 1.5- and 4-hours post-dose at study weeks 2, 10, and 24, with C0 samples at weeks 6 and 16. ABC concentrations were measured by LC-MS/MS and ABC PK parameters estimated using a population approach. Adverse events (AE) were evaluated from entry to week 24.
Twenty-five infants (18 LBW) were included in the analysis. Median entry age was 44 days (range 11 to 78 days). Twelve (48%) infants were male and 22 (88%) black African. Median ABC dose was 10 (6-13) mg/kg BID and ABC concentrations were available for 24 (195 observations) infants with median (range) birth weight 2190 g (1360-3260) and median gestational age 36 weeks (32-37). ABC plasma concentrations were described by a 1-compartment model. Infant body weight (BW) and post-menstrual age (PMA=gestational age+postnatal age [PNA]) influenced ABC PK parameters. ABC oral clearance (CL/F) increased by 2% per PMA week. Infant characteristics and ABC PK parameters per PK visit are shown in Table 1. One infant died of unknown cause 3 days after entry. Fourteen infants had Grade 3/4 AEs, among which most common were gastroenteritis (n=4) and respiratory infection (n=4) and all of which improved except for malnutrition (n=1), underweight (n=1) and a respiratory infection (n=1) present at the last study visit. No hypersensitivity was reported. All AEs were assessed as unrelated to ABC, except for one possibly related Grade 2 alanine aminotransferase where all antiretrovirals were stopped for 2 weeks until resolution then restarted without further complications.
ABC was well tolerated in LBW infants. ABC exposures were relatively high compared to older infants during the first 3 months of life but decreased rapidly as infants matured.