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VIRAL CONTROL INDUCED BY HIVCONSV VACCINES & ROMIDEPSIN IN EARLY TREATED INDIVIDUALS
Beatriz Mothe1, José Moltó2, Christian Manzardo3, Josep Coll1, Maria C Puertas1, Javier Martinez-Picado1, Tomas Hanke4, Bonaventura Clotet1, Christian Brander1
1IrsiCaixa AIDS Rsr Inst, Badalona, Spain,2Fundació Lluita Contra la Sida, Badalona, Spain,3Univ of Barcelona, Barcelona, Spain,4The Jenner Inst, Oxford, UK
The combined use of therapeutic vaccination and specific drugs that can reactivate latent reservoir virus (Kick and kill strategies) hold the promise to achieve a functional cure for HIV infection. The recently completed BCN01 vaccine trial (NCT01712425) consisted in a ChAd.HIVconsv and MVA.HIVconsv prime/boost vaccination in early treated individuals (<6 months from HIV acquisition) and was able to redirect CTL responses towards highly conserved regions of HIV-1. Likewise, romidepsin (RMD) has been shown in earlier studies to induce HIV-1 transcription demonstrating that significant reversal of HIV-1 latency is possible so that a combination of these two approaches may help achieve the goal of a functional cure of HIV.
BCN02-Romi (NCT02616874) is an ongoing single-arm proof-of-concept study enrolling 15 individuals rolled-over from BCN01 trial. After 3 years under viral suppression, all participants were immunized with MVA.HIVconsv (2x10E8 pfu), followed by three weekly-doses of romidepsin (RMD, 5 mg/m2 BSA), and by a second MVA.HIVconsv vaccination. Participants underwent a monitored antiretroviral pause (MAP) and treatment was resumed if plasma viral load (pVL) increased >2,000 copies/ml.
15 participants completed all immunizations and RMD infusions, with pVL >20 copies/ml being detected during the intervention in all of them. After the first MVA.HIVconsv vaccination, HIVconsv-specific T cell responses raised to a median peak magnitude of 965 IFNg SFC/10E6 (range 400-3,340, in cryopreserved-and-thawed PBMC), which was significantly higher (p=0.0353) than peak responses during BCN01. Responses transiently decreased by 35% in magnitude after RMD in 10 individuals. However, all but two participants were able to maintain or increase HIV-consv specific responses after the 2nd vaccination relative to pre-RMD, and were therefore invited to start the MAP. To date, 11 patients have interrupted treatment: 7 had to resume cART within the first 4 wk of MAP while 4 participants remain off cART after 7, 12, 14 and 22 weeks (36% of viremic controllers)
Therapeutic vaccination targeting conserved regions of HIV-1 combined with HIV latency reactivation strategies may facilitate clearance of the viral reservoir in early-treated individuals. This is the first reported immune intervention demonstrating a manipulation of the CTL immunodominance pattern and a durable viremic control of HIV-1 infection in a large proportion of participants.