CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

ATV or RTV-boosted DRV plus 2 NRTIs. The adult dosage of COBI 150 mg was administered and plasma exposures of ATV and DRV were evaluated by intensive PK on Day 10. We report data from Part A, in which all participants participated in intensive PK sampling and were followed through Week 12. Results: We enrolled 22 adolescents; median age 14 years (range 12-17), median body weight 52.7 kg, 36% female, 23% Black, mean CD4 count 989 cells/μL. Participants received COBI with ATV (n=14) or DRV (n=8). In adolescents (vs adult historical intensive PK data), steady-state plasma exposures of ATV and DRV were modestly higher (24-71%) (ATV) or similar (DRV), except DRV C tau was slightly lower when combined with COBI (Table). Exposures to both protease inhibitors fell within safe and efficacious ranges of adults. No participant experienced treatment-related serious adverse events (AEs) or AEs leading to study drug discontinuation. Small decreases in eGFRSchwartz (median -6.7 mL/ min/1.73m 2 ) were seen at Week 12, consistent with the inhibitory effect of renal creatinine secretion by COBI. Most participants, 21 of 22 (95%), had HIV-1 RNA <50 c/mL at Week 12. Conclusion: In adolescents, when boosted with adult dosage strength of COBI, plasma exposures of ATV and DRV were within safe and efficacious ranges as seen in adults. Virologic suppression was maintained and treatment was generally well tolerated through 12 weeks. These findings support ongoing evaluation of COBI 150 mg as a pharmacoenhancer of ATV or DRV in adolescents 12 to <18 years of age.

Poster and Themed Discussion Abstracts

426 EFFECT OF DOLUTEGRAVIR PLASMA CONCENTRATION ON CENTRAL NERVOUS SYSTEM SIDE EFFECTS Hiroki Yagura 1 , Dai Watanabe 1 , Takao Nakauchi 1 , Kosuke Tomishima 1 , Daisuke Kasai 1 , Yasuharu Nishida 1 , Munehiro Yoshino 2 , Tomoko Uehira 1 , Kunio Yamazaki 1 , Takuma Shirasaka 1 1 Natl Hosp, Osaka, Japan, 2 Natl Hosp Org Osaka Minami Med Cntr, Osaka, Japan Background: Dolutegravir (DTG), a second-generation HIV integrase inhibitor that can easily be administered once daily, was shown to have apparent non-inferior efficacy in comparison with other medications in phase III trials. At present, it is being prescribed increasingly, especially in developed countries, including Japan, and has been previously reported to induce side effects in the central nervous system (CNS), such as insomnia and headache. However, its mechanism including association between DTG plasma concentration and CNS side effects remains unknown. Methods: We recruited 162 HIV-infected patients who had undergone anti-retroviral treatment, including DTG treatment, from Osaka National Hospital, Japan, from April 2014 to March 2016. DTG plasma trough concentration was measured, and the association between DTG concentration and CNS side effects was statistically analyzed within 6 months of DTG introduction. Results: Of the 162, 154 (95%) were male and 8 (5%) were female. Their age at enrollment was median 43 years old (inter quartile range 38-52). 36 (22%) patients introduced DTG in the first antiretroviral treatment.In the rest of 126 (78%), DTG was switched from other antiretroviral agents. At least one of the CNS side effects was observed in 41 (25%) patients, which include dizziness [14/41 (34%)], headache [11 (27%)], insomnia [11 (27%)], restlessness [4 (10%)], and anxiety [3 (7%)]. According to the analyses: 1) patients with CNS side effects scored higher trough DTG plasma concentration compared with the subjects without symptoms (median 1.34 vs 1.03 ug/ml, p=0.003 by univariate Mann-Whitney U-test, and p=0.005 by multivariate binary regression test); 2) positive correlation was observed between DTG concentration and frequency of CNS side effects (p=0.002;Figure) ; and 3) no significant difference in DTG concentration was observed among CNS symptoms (p=0.56). Conclusion: In this study, a positive correlation between trough plasma DTG concentration and CNS side effects was identified among Japanese population. This implied the importance of DTG concentration measurement for the evaluation of CNS side effects.

CROI 2017 177