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
Last update: 05/09/2017

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) and patient disposition

Primary endpoint: HIV RNA < 50 c/mL at W32 (snapshot analysis, ITT-ME)

  • Non inferiority of the 2 IM regimens vs oral CAB

HIV RNA < 50 c/mL at W48 and W96 (snapshot analysis, ITT-ME)


  • Non inferiority of the 2 IM regimens vs oral CAB, at W48 and W96
  • Lower performance of Q4W (vs Q8W) at W96 due to more discontinuations for AE (9 vs 1)
  • Protocol-defined virologic failure: 1 in oral arm (no resistance), 2 in Q8W arm (emergence of resistance at failure: K103N, E138G, K238T (NNRTI) and Q148R (INSTI) in 1, R269R/G in 1

Virologic non response and no data in window (snapshot analysis at W96)

* Rash, N = 1, liver stopping criteria, N = 1, QT prolongation, N = 1, mesenteric vein thrombosis, N = 1, Churg-Strauss vasculitis, N = 1, epilepsy leading to death, N = 1, psychosis, N = 1, depression, N = 1, hepatitis C, N = 1
** Acute hepatitis C, N = 1, liver stopping criteria, N = 1
*** Withdrawal by subject, N = 3 ; protocol deviation, N = 2
**** Withdrawal by subject, N = 5 ; lost to follow-up, N = 1

Adverse events and laboratory abnormalities (ITT, maintenance period D0-W96), %


* Influenza-like illness, N = 1, chills and pain, N = 1
** Influenza-like illness, N = 1, rash, N = 1, depression, N = 1, QT prolongation, N = 1
*** ISR = pain (66%), nodules (8%), swelling( 6%), pruritus (6%), resolved < 7 days: 89%

Overall injection site reaction incidence, by visit Day 1-Day 96 (% patients with ISR)


  • 99% of ISRs were mild (84%) or moderate (15%)
  • Median duration was 3.0 days in both groups, and 89% resolved within 7 days
  • Most common ISR events : pain (66%), nodules (8%), swelling (6%) and pruritus (6%)
  • The number of subjects reporting ISRs decreased over time, from 86% (D1) to 35% (W48) and 30% (W96)
  • 2/230 subjects (< 1%) withdrew as a result of injection reactions (both in Q8W group)

Pharmacokinetics (mean + SD plasma concentration (mg/mL)


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

Patient reported-outcomes (HIV Treatment satisfaction questionnaire, status version)


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