001). Baseline INSTI resistance (genotypic and phenotypic) and baseline viral load were highly significant predictors of response at week 24. For every twofold increase in DTG change, the odds of virologic suppression to <50 copies/mL were 63% lower, and were 96% lower if the virus contained Q148 +≥2 mutations. VIKING 4 (unpublished; NCT01568892) is designed similar to VIKING 3, but with a randomized (1:1), double-blind placebo study

design to quantitatively evaluate antiviral activity specifically attributed to DTG [37]. Results of this study are not yet published. Pediatric Formulations IMPAACT study P1093 (NCT01302847) is an ongoing Phase I/II safety and dose-finding study for treatment-experienced, INSTI-naïve infants, children and adolescents. Similar to the VIKING studies, DTG is first added to a failing regimen for 5–10 days, then OBR for further follow-up. CAL-101 solubility dmso This study is composed of five age-related cohorts ranging from >6 weeks up to 18 years. Data for the oldest two cohorts have been presented at scientific meetings [38–40]. The first cohort >12 and <18 years provided data contributing to the FDA label approving DTG down to 12 years of age with a weight minimum of 40 kg [24]. These pediatric studies measure virologic suppression <400 copies/mL SBI-0206965 in vivo at 24 weeks (83%) [38] and 48 weeks

(74%) with an additional secondary endpoint as <50 copies/mL (70% and 61%, respectively) [39]. Virologic failure (<400 copies/mL) at week 48 in all 6 of 23 adolescents was attributed to incomplete

adherence based on a 3-day pill recall questionnaire. There were no DTG drug-related adverse Protirelin events and no discontinuations. The target area under the curve at 24 h (AUC24) and concentration at 24 h (C24) were achieved with ~1 mg/kg dosing [39, 40]. A pediatric granule formulation has been developed and tested, demonstrating that drug exposure exceeds that of the tablet form, is palatable, and can be given without food or liquid restrictions [41]. Adverse Events and Side Effects Creatinine typically rises in the first 2 weeks after starting DTG, returning to baseline by 48 weeks [27, 29]. This rise in creatinine is attributed to DTG’s potent inhibition of human organic cation transporter (OCT2) that inhibits proximal renal tubular creatinine secretion without affecting GFR, similar to other drugs including trimethoprim and cimetidine [42]. Approximately 1.7% of aggregate participants in cited clinical trials experienced increased ALT levels (>5× the normal limit) with approximately three participants (~0.2%) with evidence of DILI, possibly attributed to DTG [23, 28, 29, 32, 35]. These findings have mostly been explained by the inclusion of participants co-infected with hepatitis B and/or hepatitis C, who experience immune check details reconstitution inflammatory syndrome (IRIS) attributed to the potency of DTG.