Dolutegravir exposure comparable with vs without food in children with HIV

Dolutegravir (DTG) as second-line treatment for children with HIV infection results in comparable drug exposure levels when taken with vs without food, according to study findings published in Clinical Infectious Diseases.

Researchers conducted a nested pharmacokinetic (PK) substudy among HIV-positive children enrolled in the CHAPAS4 trial, an ongoing randomized controlled trial designed to investigate second-line treatment options for HIV infection. The researchers aimed to evaluate drug exposure levels among children receiving DTG with food. Children weighing between 14 and 19.9 kg received 25-mg dispersible tablets of DTG, and those weighing 20 kg and above received 50-mg film-coated tablets of DTG. Steady-state 24-hour DTG plasma concentration-time PK profiling was performed at various time points (0, 1, 2, 4, 6, 8, 12, and 24 hours) after intake of DTG with food. Reference PK data from adult and pediatric patients enrolled in the ODYSSEY trial was used for comparison. The individual target trough concentration (C_trough) was set at 0.32 mg/L.

The final analysis included 39 children with evaluable PK profiles, of whom the median age was 10.8 years, 54% were boys, and the median weight was 27.0 kg.

In regard to DTG exposure levels among children who received treatment with food, the geometric mean area under the concentration-time curve (AUC_0-24h) was 57.1 h*mg/L. The researchers noted that this value was 8% lower than the AUC_0-24h observed among children who received comparable DTG dosages with food, but 32% higher than the AUC_0-24h observed among adults who received DTG 50 mg once daily with food. In addition, the geometric mean (coefficient of variation) C_trough was 0.82 mg/L (63.8%) among children who received DTG with food, which was similar to that of adult and pediatric references who received DTG without food.

The median time to reach the maximum plasma concentration (T_max) among children who received DTG without food was 2 hours less than that of the median T_max observed among children and adults who received DTG with food.

Stratified by weight bands, the highest drug exposure levels among children who received DTG without food were observed among those weighing between 20 and 24.9 kg.

Receipt of DTG as dispersible vs film-coated tablets did not significantly affect drug exposure levels.

There was 1 child in the PK substudy who did not achieve the C_trough target following treatment with DTG in combination with emtricitabine plus tenofovir alafenamide. As a limitation to this study, the researchers were unable to relate lower DTG exposure in this patient to virologic efficacy since the CHAPAS4 trial is ongoing.

According to the researchers, “Our data suggest that the influence of food on DTG exposure in Children might be less pronounced than in adults, suggesting that DTG can be taken safely with or without food by children.”

Disclosure: This research was supported by ViiV Healthcare, Janssen Pharmaceuticals, and Gilead Sciences Inc., and multiple study authors declared affiliations with industry. Please see the original reference for a full list of disclosures.

By Lisa Kuhns, PhD

References:

Bevers L, Waalewijn H, Szubert A, et al. Pharmacokinetic data of dolutegravir in second-line treatment of children living with HIV: results from the CHAPAS4-trial. Clin Infect Dis. Published online June 6, 2023. doi:10.1093/cid/ciad346