Abstract Body

Background: Cabotegravir (CAB, GSK744) is an HIV INSTI under development as both an oral and long-acting (LA) injectable. LATTE was designed to select an oral dose of CAB and to evaluate a two-drug ART regimen with rilpivirine (RPV), as suppressive maintenance therapy.

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 mg, 30 mg, 60 mg or efavirenz (EFV) 600 mg with TDF/FTC or ABC/3TC through Week (W) 24, followed by a two-drug oral maintenance regimen of CAB (blinded dose) + RPV 25 mg through W96. CAB patients (pts) with a VL <50 c/mL immediately prior to W24 discontinued NRTIs and began RPV 25 mg; no change was made for EFV + NRTIs pts (ITT-Maintenance Exposed (ME)).

Results: 243 pts were randomized and treated (ITT-E): 96% male, 38% non-white, 14%>100,000 c/mL HIV-1 RNA, 61% TDF/FTC. Amongst pts who began CAB + RPV at W24, 86% had HIV-1 RNA <50 c/mL by snapshot at W96 overall, relative to 83% of pts continuing EFV (ITT-ME). Five protocol-defined virologic failures occurred during 72 weeks of Maintenance (CAB 10 mg [2], CAB 30 mg [1], EFV [2] including two on CAB + RPV with treatment emergent resistance [INI + NNRTI, NNRTI]). Drug-related AEs ≥ Grade 2 were reported by 14% and 19% of CAB and EFV pts, respectively with 4% and 4% occurring during the 72W Maintenance phase. SAEs occurred in 10% of CAB pts (none drug related); and 6% EFV pts (one drug-related – suicide attempt). Fewer CAB pts withdrew due to AEs (3%), than EFV pts (15%), mostly prior to the Maintenance phase. Treatment-emergent lab abnormalities ≥ Grade 3 occurred in 26% of CAB and 37% of EFV pts through W96, most commonly elevated creatine kinase. Rates of any graded ALT elevations were 20% with CAB and 21% with EFV.

Conclusions: When used as two-drug maintenance therapy in virologically suppressed pts, CAB + RPV provided similar antiviral activity to EFV+2 NRTIs through W96. CAB + RPV was well tolerated overall, with no SAEs considered drug related and few AEs leading to withdrawal. Considering all safety and efficacy data, oral CAB 30mg once-daily was selected for further development. Results support the selected dose regimens for the ongoing Ph2 LATTE-2 study with CAB LA + RPV LA as injectable two-drug maintenance therapy.

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Snapshot Study Outcomes CAB
⇥⇥⇥10 mg
⇥⇥⇥(n=60)
CAB
⇥⇥⇥30 mg
⇥⇥⇥(n=60)
CAB
⇥⇥⇥60 mg
⇥⇥⇥(n=61)
CAB
⇥⇥⇥Subtotal
⇥⇥⇥(n=181)
EFV
⇥⇥⇥Control
⇥⇥⇥(n=62)
%<50c/mL at W96 Snapshot (ITT-E) (95%CI)++ 41 (68%)
⇥⇥⇥(57%,80%)
45 (75%)
⇥⇥⇥(64%,86%)
51 (84%)
⇥⇥⇥(74%,93%)
137 (76%)
⇥⇥⇥(69%,82%)
39 (63%)
⇥⇥⇥(51%,75%)
Protocol-defined Virologic Failure 3 (5%) 2 (3%) 1 (2%) 6 (3%) 6 (10%)
Failure due to Adverse Event 1 (2%) 1 (2%) 4 (7%) 6 (3%) 9 (15%)
Failure due to HIV-1 RNA ≥50 c/mLÂ¥ 5 (8%) 1 (2%) 2 (3%) 8 (4%) 2 (3%)
Failure due to Other Reasons While Not Suppressed+ 2 (3%) 2 (3%) 1 (2%) 5 (3%) 3 (5%)
Failure due to Other Reasons While Suppressed+ 8 (13%) 9 (15%) 2 (3%) 19 (10%) 3 (5%)
Other Results
<50 c/mL at W96 Snapshot (ITT-ME) 41/52
⇥⇥⇥(79%)
45/53
⇥⇥⇥(85%)
51/55
⇥⇥⇥(93%)
137/160
⇥⇥⇥(86%)
39/47*
⇥⇥⇥(83%)
Grade 2-4 Drug Related AEs 5 (8%) 8 (13%) 13 (21%) 26 (14%) 12 (19%)
Median Baseline CD4+ cells/mm3 (Change from Baseline at W96) 415.0
⇥⇥⇥(236.5)
404.0
⇥⇥⇥(249.5)
420.0
⇥⇥⇥(271.5)
412.0
⇥⇥⇥(259.5)
416.5
⇥⇥⇥(289.0)
Â¥ HIV-1 RNA ≥50 c/mL reasons include HIV-1 RNA ≥50c/mL at Week 96 or discontinued while not suppressed (≥50 c/mL) for Lack of Efficacy
⇥⇥⇥+ Other reasons include missing data; protocol deviation, non-compliance, lost to follow-up, withdrawn consent, investigator discretion, ART change, and ineligible for Maintenance phase
⇥⇥⇥++W96 represents a 24 Week Induction phase followed by a 72 Week Maintenance phase
⇥⇥⇥*EFV pts with a W24 visit (n=47)
⇥⇥⇥Intent to Treat-Exposed (ITT-E) and Intent to Treat- Maintenance Exposed (ITT-ME)