Session: 262. HIV: Antiretroviral Therapy, Saturday, 12:15-1:30 p.m.
Monthly injectable CAB LA + RPV LA was noninferior to daily oral 3-drug antiretroviral therapy in HIV-1 virologically suppressed adults. CAB and RPV pharmacokinetics (PK) were assessed during the 48 Wk maintenance period of the ATLAS and FLAIR Phase 3 studies.
Methods : Patients received oral CAB 30mg + RPV 25mg once daily for 4 weeks to assess individual tolerability prior to intramuscular (IM) injections of CAB LA 600mg + RPV LA 900mg followed by CAB LA 400mg + RPV LA 600mg every 4 weeks. Plasma CAB and RPV concentrations were measured pre-and post-dose at select visits using validated analytical methods.
Results : Baseline demographics for the pooled randomized ATLAS and FLAIR population (n=591, LA arms) were: median age 38 years, 27% female, 18% African American, median BMI 25 kg/m2 (range: 15 – 51). CAB and RPV plasma concentrations at select visits are summarized in the table. After initial IM doses, mean CAB and RPV troughs were well above their respective in vitro PA-IC90 values (CAB, 0.166 mcg/mL; RPV 12 ng/mL). At Wk 48, mean CAB troughs were 17x PA-IC90 and between oral CAB 10-30mg exposures. Similarly, mean RPV troughs were 7x PA-IC90 and remained within the exposure range following oral RPV 25mg once daily. 80% of RPV steady-state was achieved by Wk 48 and 100% for CAB by Wk 44. Initial CAB concentrations in females and those with BMI≥30 kg/m2 were lower due to slower absorption but this difference resolved by Wk 48. For RPV, there was no absorption difference by gender or BMI.
Conclusion : CAB and RPV PK were consistent between studies achieving therapeutic concentrations within the first dosing interval that steadily increased over time through Wk 48, for both males and females and irrespective of BMI. CAB LA + RPV LA provided compatible PK profiles following monthly IM dosing in a diverse patient population through 48 weeks.
Parul Patel– Director, Clinical Pharmacology, ViiV Healthcare, Research Triangle Park, NC
Susan Ford– Director, GlaxoSmithKline, Research Triangle Park, NC
Herta Crauwels– Associate Director Clinical Pharmacology, Janssen Research and Development, Antwerpen, Oost-Vlaanderen, Belgium
Kelong Han– Director, GlaxoSmithKline, Collegeville, PA
Stefaan Rossenu– Scientific Director, Janssen Research and Development, Beerse, Antwerpen, Belgium
Martine Neyens– Senior Associate Scientist, Janssen Research and Development, Beerse, Antwerpen, Belgium
Sandy Griffith– Director Clinical Development, ViiV Healthcare, Research Triangle Park, NC
Krischan Hudson– Director of Clinical Development, ViiV Healthcare, Research Triangle Park, NC
David Margolis– Director of HIV Drug Development, ViiV Healthcare, Research Triangle Park, NC
Mark Baker– Director, Clinical Pharmacology, ViiV Healthcare, Nyon, Vaud, Switzerland
Peter Williams– Dr, Janssen Research & Development, LLC, Beerse, Antwerpen, Belgium
William Spreen– R&D, Medicine Development Leader, ViiV Healthcare, Research Triangle Park, NC