CROI 2017 Abstract e-Book

Abstract eBook

Oral Abstracts

119LB VIRAL CONTROL INDUCED BY HIVCONSV VACCINES & ROMIDEPSIN IN EARLY TREATED INDIVIDUALS Beatriz Mothe 1 , José Moltó 2 , Christian Manzardo 3 , Josep Coll 1 , Maria C. Puertas 1 , Javier Martinez-Picado 1 , Tomas Hanke 4 , Bonaventura Clotet 1 , Christian Brander 1 , for the BCN02- Romi Study Group 1 IrsiCaixa AIDS Rsr Inst, Badalona, Spain, 2 Fundació Lluita Contra la Sida, Badalona, Spain, 3 Univ of Barcelona, Barcelona, Spain, 4 The Jenner Inst, Oxford, UK Background: 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. Methods: 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. Results: 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) Conclusion: 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.

Oral Abstracts

120 NO EVIDENCE OF ONGOING HIV REPLICATION AFTER 7 YEARS ON ART Mary Grace K. Katusiime 1 , Gert U. van Zyl 1 , Ann Wiegand 2 , Elias K. Halvas 3 , Valerie F. Boltz 2 , Barbara Laughton 1 , Susan Engelbrecht 1 , Mark Cotton 1 , John W. Mellors 3 , Mary F. Kearney 2 1 Stellenbosch Univ, Parow, South Africa, 2 NCI, Frederick, MD, USA, 3 Univ of Pittsburgh, Pittsburgh, PA, USA Background: Although a long-term study of clinically-effective ART showed no evidence of HIV evolution in 13 of 14 adults (Kearney, 2014), a recent study (Lorenzo-Redondo, 2016) of 3 persons concluded that HIV evolution occurs on ART at a rate of 6x10^-4 to 1x10^-3 mutations/site/month due to ongoing viral replication in the lymph nodes with subsequent trafficking of newly infected T-cells to blood. We therefore looked for evidence of HIV evolution in children on long-term suppressive ART. ... Methods: We studied children initiated on continuous ART in the CHER study (Cotton, Lancet 2013). Samples obtained near ART initiation and after 7 years of ART underwent single-genome sequencing of the p6-PR-RT region of the HIV genome. Sequences from each time point were compared for evidence of evolution by multiple, sensitive Methods: 1) calculation of average pairwise distance (APD) for sequence diversification, 2) panmixia testing for sequence divergence, and 3) construction of maximum-likelihood (ML) trees to measure root-to-tip distances for emerging new variants. Results: 12 children were studied: 10 who started ART ≤ 1 year and had viremia suppressed on ART for 7 years and 2 “replication-controls” who had viremia for 1-3 years prior to or during ART. All children had very low viral diversity (median of 0.3%) at the time of ART initiation (Table), providing a low background on which to detect evolution. The 2 replication-controls showed obvious evidence of HIV evolution: increased viral diversity, a significant virus population shift by panmixia (Table), and longer root-to-tip distances in ML trees. In 8 of 10 children, there was no evidence of viral divergence on ART. A significant virus population shift by panmixia occurred in 1 child (PID 8) who had decreasing branch lengths on the ML tree suggesting decay of infected cells on ART. Another child (PID 9) with an HIV RNA blip to 56 copies/ml had a marginally significant shift in the virus population by panmixia from possible ongoing viral replication. The absence of viral evolution in 9 of 10 children is inconsistent with the 5-8% divergence expected from ongoing replication over 7 years predicted by Lorenzo-Redondo et al. Conclusion: These data from early ART-treated children strongly refute the concepts that ongoing HIV replication is common on current ART regimens and that it replenishes the HIV reservoir.

47

CROI 2017