Background.We evaluated dolutegravir pharmacokinetics in infants with human immunodeficiency virus (HIV) receiving dolutegravir twice daily (BID) with rifampicin-based tuberculosis (TB) treatment compared with once daily (OD) without rifampicin. Methods. Infants living with HIV aged 1-12 months, weighing >= 3kg, and receiving dolutegravir BID with rifampicin or OD without rifampicin were eligible. Six blood samples were taken over 12 (BID) or 24 hours (OD). Dolutegravir pharmacokinetic parameters, HIV viral load (VL) data, and adverse events (AEs) were reported. Results. Twenty-seven of 30 enrolled infants had evaluable pharmacokinetic curves. The median (interquartile range) age was 7.1 months (6.1-9.9), weight was 6.3 kg (5.6-7.2), 21 (78%) received rifampicin, and 11 (41%) were female. Geometric mean ratios comparing dolutegravir BID with rifampicin versus OD without rifampicin were area under curve (AUC)(0-24h) 0.91 (95% confidence interval, .59-1.42), C-trough 0.95 (0.57-1.59), C-max 0.87 (0.57-1.33). One infant (5%) receiving rifampicin versus none without rifampicin had dolutegravir C-trough <0.32mg/L, and none had C-trough <0.064mg/L. The dolutegravir metabolic ratio (dolutegravir-glucuronide AUC/dolutegravir AUC) was 2.3-fold higher in combination with rifampicin versus without rifampicin. Five of 82 reported AEs were possibly related to rifampicin or dolutegravir and resolved without treatment discontinuation. Upon TB treatment completion, HIV viral load was <1000copies/mL in 76% and 100% of infants and undetectable in 35% and 20% of infants with and without rifampicin, respectively. Conclusions. Dolutegravir BID in infants receiving rifampicin resulted in adequate dolutegravir exposure, supporting this treatment approach for infants with HIV-TB coinfection.

INTRODUCTION:An adverse event following immunisation is any untoward medical occurrence which follows vaccination. Frequency of adverse events ranges from 13% to 34% and they should be reported regardless of severity. From the beginning of 2016 to mid-2017, Guruve district in Zimbabwe did not report any AEFIs. This suggests the surveillance system may be failing to detect adverse events. We therefore evaluated the AEFI surveillance system in Guruve district.METHODS:We conducted a surveillance system evaluation using the updated Centers for Disease Control guidelines for evaluating public health surveillance systems. We interviewed health workers and caregivers of babies under 2 years in Guruve district. We also reviewed all records on AEFI surveillance for the period of January 2016 to November 2017.RESULTS:We recruited 31 health workers and 33 caregivers into the study. Between January 2016 and mid-2017, 39% of the caregivers had children who had suffered AEFIs and 45% of the health workers had encountered AEFIs but none had been notified. The main reasons for failure to report AEFIs included health workers' fear of personal consequences and caregivers thinking that an adverse event was not serious enough to report. Knowledge of the surveillance system was good amongst the majority of health workers. All the resources needed by the surveillance system were available.CONCLUSION:We concluded that health workers in Guruve district were afraid to report adverse events following immunization and caregivers were reluctant to report mild adverse events hence the surveillance system was performing poorly and was not useful. However, the stability of the system and the good knowledge gives a good foundation for improving the surveillance system.