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Early treatment initiation: RV254/SEARCH 010 Study Group

Early treatment initiation: RV254/SEARCH 010 Study Group . Jintanat Ananworanich on behalf of the RV254/SEARCH 010 Study Group Jintanat.A@SearchThailand.org. Almost all Fiebig I patients had undetectable integrated HIV DNA in peripheral blood mononuclear cells during acute HIV. 92%.

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Early treatment initiation: RV254/SEARCH 010 Study Group

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  1. Early treatment initiation: RV254/SEARCH 010 Study Group Jintanat Ananworanich on behalf of the RV254/SEARCH 010 Study Group Jintanat.A@SearchThailand.org

  2. Almost all Fiebig I patients had undetectable integrated HIV DNA in peripheral blood mononuclear cells during acute HIV 92% 53% Ananworanich J, et al. 2013 CROI (abstract 47)

  3. Almost all subjects treated during acute HIVhad undetectable integrated HIV DNA after one year of antiretroviral treatment 100% 89%

  4. Integrated HIV DNA at time of acute HIV infection Not detected Not detected Not detected Fiebig I Fiebig III Ananworanich J, et al. 2013 CROI (abstract 47)

  5. Integrated HIV DNA at 24 weeks after ART Not detected Not detected Fiebig I Fiebig III Chronic HIV

  6. MegaHAART vs. HAART Randomization (24 wks) TDF + 3TC/FTC + EFV + RAL + MVC vs. TDF + 3TC/FTC + EFV Followed by TDF + 3TC/FTC + EFV Total HIV DNA 2 LTR circles Integrated HIV DNA

  7. Half of Fiebig I subjects have non-reactive 2nd generation EIA and/or Western Blot at 24 weeks after ART Non-reactive 2nd generation EIA Non-reactive/IND Western Blot CD4/CD8 ratio ≥ 1 Wk 0: 88% in Fiebig I vs. 20% in Fiebig III, p < 0.001 Wk 24: 64% in Fiebig I vs. 54% in Fiebig III, p = 0.6

  8. Frequency of Gag-specific IFN-gamma response and number of respondersat baseline and 24 weeks after ART in the periphery CD4 CD8 6/30 (20%) 2/17 (12%) 4/30 (13%) 11/17 (65%) Number of responders

  9. Using 4th Generation (Ag-Ab combo) Enzyme Immunoassay to distinguish two groups of Fiebig I subjects Ananworanich J, et al. Retrovirology 2013

  10. Hypothesis 1 Is early ART alone sufficient to cure in patients treated during Fiebig I? Hypothesis 2 Will therapeutic HIV vaccine + early ART result in better viremic control vs. early ART alone? Where we are now in RV254/ SEARCH 010 ART initiated during acute HIV restricted infection in PBMCs and TCM A series of randomized trials are being developed Goal Functional cure (Viremic control without ART) Hypothesis 3 Will HDACi + early ART result in depletion of reservoir/cure vs. early ART alone? Hypothesis 4 Will anti-inflammatory drugs + early ART result in less immune activation and reservoir vs. early ART alone?

  11. RV254/SEARCH 010 Acknowledgement Thai Red Cross/Chula Volunteers Funding from US Military HIV Research Program MHRP • Nelson Michael • Jerome Kim • Merlin Robb • HendrikStreeck • Diane Bolton • Bonnie Slike • SodsaiTovanabutra • Gustavo Kijak • Jean-Louis Excler • Praphan Phanuphak • Kiat Ruxrungtham • Mark de Souza • Frits van Griensven • Thep Chalermchai • James LK Fletcher • Eugene Kroon • Nipat Teeratakulpisarn • Rungsun Rerknimitr • Wiriyaporn Ridtitid • SukalyaLerdlum • Supranee Buranapraditkun • Duanghathai Suttichom • Somprartthana Rattanamanee • Peeraya Mangu • Sasiwimol Ubolyam • Mantanapothisri • Phandee Wattanaboonyongcharoen • Ponlapat Rojnuckarin • Sopark Manasnayakorn • Suteeraporn Pinyakorn AFRIMS Thai GPO (TDF, 3TC, EFV, LPV/r) Gilead (TDF, FTC) Merck (EEV, RAL) Pfizer (MVC) Monogram (Trofile) • Alexandra Schuetz • Rapee Trichavaroj • Vatcharain Assawadarachai • Yuwadee Phuangngern • Rapee Trichavaroj • Siriwat Akapirat • Nantana Tantibul • PanaddaSawangsinth • Susan Mason • Bessara Nuntapinit • Wanwarang Khobchit • Sakuna Suksawad • Ajchariyarat Sangdara • Kultida Poltavee • Hathairat Savadsuk • Suwittra Chaemchuen • Surat Jongrakthaitae • ChayadaSajiaweerawan • NipattraTragonlugsana • PutidaSaetun NIAID • Irini Sereti • Daniel Douek • Netanya Sandler • Mary Marovich NCI • Jacob Estes • Robin Dewar • Adam Rupert SAIC-Frederick UCSF Yale • Frank Maldarelli • Mary Kearney • Ann Wiggins Industry • Victor Valcour VGTI • Serena Spudich • Idil Kore UMN • Nicolas Chomont • Claire Vandergeeten • Rafick Sekaly • Elias Haddad • Lydie Trautmann Huntington Memorial • Timothy Schacker • Napaporn Sailasuta

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