C1. Clinical trials (abstracts submitted to C1 should choose a secondary category that describes the subject matter of the trial)
Oral Abstract Submission
David Margolis, MD, MPH
Director of HIV Drug Development
Research Triangle Park, NC
Disclosure: ViiV Healthcare: Employee, Shareholder, Other Financial or Material Support, Salary and stock options
Edwin DeJesus, MD
Orlando Immunology Center, University of Central Florida College of Medicine
Disclosure: Gilead Sciences: Scientific Research Study Investigator, Advisor or Review Panel member, Research Grant or Support
Janssen Infectious Diseases: Scientific Research Study Investigator, Advisor or Review Panel member
Merck: Scientific Research Study Investigator
Theratechnologies: Scientific Research Study Investigator, Advisor or Review Panel member
ViiV Healthcare: Scientific Research Study Investigator
Anthony Mills, MD
Chief Medical Officer
Men’s Health Foundation
Los Angeles, CA
Disclosure: Gilead: Grant/Research Support, Advisor or Review Panel member
Janssen: Grant/Research Support, Advisor or Review Panel member
Merck: Grant/Research Support, Advisor or Review Panel member
ViiV Healthcare: Grant/Research Support, Advisor or Review Panel member
Jean-Guy Baril, MD
Clinique Medicale Quartier Latin
Montreal, QC, Canada
Disclosure: Gilead: Consultant, Grant/Research Support
ViiV Healthcare: Board Member, Consultant, Grant/Research Support
Background : Cabotegravir (CAB), an INI, is under development in both oral and long-acting (LA) injectable formulations. LATTE (NCT01641809) was designed to select a daily oral dose of CAB and evaluate a two drug ART regimen with rilpivirine (RPV), as suppressive maintenance therapy. Results enabled the LATTE-2 (NCT02120352) study to evaluate CAB LA + RPV LA dosed once every 1 or 2 months.
Methods : Phase 2b, multicentre, partially-blinded dose-ranging study in ART-naïve HIV infected adults, randomized 1:1:1:1 to the induction regimen of once daily oral CAB 10, 30, or 60 mg or efavirenz (EFV) 600 mg with TDF/FTC or ABC/3TC through W24. CAB patients (pts) with VL <50 c/mL immediately prior to W24 discontinued NRTIs and began RPV 25 mg as a two-drug oral maintenance regimen through W96. No change was made to the EFV arm. After W96, at the start of the open-label (OL) phase, all pts randomized to CAB were given the option to continue and switch to the sponsor-selected dose of oral CAB 30 mg. EFV pts completed the study at W96. The OL phase was completed at W312 (288 weeks on CAB + RPV). Successful CAB + RPV pts transitioned to the POLAR study (NCT03639311).
Results : 243 pts were randomized and initiated treatment (ITT-E). Of those randomized to CAB (n=181), 160 pts began CAB + RPV (W24) and 138 continued into OL phase (W96). 110 pts successfully completed the study (W312). Among pts who began CAB + RPV at W24, 66% maintained <50 c/mL, 9% had HIV-1 RNA ≥ 50 c/mL, and 25% were categorized as ‘No Virologic Data’ by Snapshot at W312 (ITT-ME). There were 11 protocol defined virologic failures (PDVF) on CAB; only 2 occurring after W144. 6 pts developed treatment emergent (TE) resistance to one or both agents during the study; of which 4 pts developed TE major INI resistance mutations, 3 after W96. Median increase in CD4+ cell count from Baseline was 393 cells/mm3 (-174–1118). During the maintenance and OL phases, 4% of CAB pts reported drug-related AEs ≥ Grade 2; SAEs occurred in 9% of CAB pts (none drug related); 3% of CAB pts withdrew due to AEs. 43% of CAB pts who entered maintenance phase reported TE lab abnormalities ≥ Grade 3.
Conclusion : As maintenance therapy in virologically suppressed pts, the 2DR CAB + RPV provided durable viral suppression through W312. Through 7 years of study, CAB + RPV continues to be generally safe and well tolerated.