Switch studies in virologically suppressed patients
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Switch to INSTI + NNRTI
LATTE-2 Study: Switch to cabotegravir LA + rilpivirine LA IM
Original article : Margolis DA. AIDS 2016, Durban, Abs. THAB0206LB
Dernière mise à jour : 29/03/2017

Dr Anton Pozniak
Chelsea and Westminster Hospital
London, UK

  • LATTE-2 results successfully demonstrate ability to maintain HIV-1 RNA < 50 c/mL with IM CAB + RPV LA, dosed every 4 or 8 weeks
  • Three subjects met PDVF criteria during maintenance
    • Q8W (N = 2), oral CAB (N = 1) ; one Q8W subject with emergent RPV and CAB resistance
  • Injection tolerability
    • Majority of ISRs were grade 1 to 2 pain, with a median duration of 3 days
    • Few subjects had an ISR that led to discontinuation
    • High overall reported satisfaction
  • Dose selection
    • Q4W dosing resulted in lower rates of virologic non-response with similar safety to Q8W
    • Q4W dosing was selected for pivotal phase III studies
    • Q8W dosing remains under evaluation within LATTE-2

Design


* CAB IM, loading dose 800 mg at D1 and 600 mg at W4
** CAB IM, loading dose 800 mg at D1
Q8W: injection every 8 weeks ; Q4W: injection every 4 weeks

Objective

  • Primary: % HIV RNA < 50 c/mL at W32 of maintenance phase: selection of dosing schedule for phase III studies (confirmation of dose on W48 analysis) ; safety

Baseline characteristics (ITT-maintenance exposed)

HIV RNA < 50 c/mL at W48 (snapshot analysis, ITT-ME)

  • Non inferiority of the 2 IM regimens vs oral CAB
  • Protocol-defined virologic failure: 2 in Q8W group, 1 in oral group
  • Emergence of resistance at failure (genotype): N = 1 (Q8W group): NNRTI (K103N, E138G, K238T), INSTI (Q148R)

Adverse events and laboratory abnormalities


a Q8W (N = 2): influenza-like illness, chills and pain; Q4W (N = 4): influenza-like illness, rash, depression, and psychosis
b one death (epilepsy).
c Q8W (N = 2): ISR, ISR/chills/body pain; Q4W (N = 7): Churg-Strauss vasculitis, hepatitis C, depression, epilepsy, psychosis, rash, and mesenteric vein thrombosis; oral CAB (N = 1): hepatitis C

Overall injection site reaction incidence, by visit (% patients with ISR)

  • 99% of ISRs were mild (82%) or moderate (17%), grade 3 were 12 in Q8W (< 1%) and 10 in Q4W (< 1%)
  • Median duration was 3.0 days in both groups, and 90% resolved within 7 days
  • Most common ISR events overall were pain (67%), nodules (7%), and swelling (6%)
  • The number of subjects reporting ISRs decreased over time, from 86% (D1) to 29% (W48)
  • 2/230 subjects (< 1%) withdrew as a result of injection reactions (Q8W)

Pharmacokinetics (mean plasma concentration ± SD)


Cτ , trough concentration ; PA-IC90, protein binding-adjusted 90% inhibitory concentration

  • Both Q4W and Q8W steady state exposures approximate once-daily oral dosing
 

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