Early treatment initiation: RV254/SEARCH 010 Study Group

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Presentation transcript:

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

history of HIV exposure 17 days Fiebig I (RNA+, p24-, 3rd gen EIA-) Characteristics (n=100) Values Median age 29 years MSM 92% Median duration from history of HIV exposure 17 days Fiebig I (RNA+, p24-, 3rd gen EIA-) Fiebig II (RNA+, p24+, 3rd gen EIA-) Fiebig III (3rd gen EIA+, WB-) 30% 15% 43% Median CD4 416 cells/mm3 Median HIV RNA 5.7 log CRF_01AE (n=62) 73% R5 tropism (n=39) 97%

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)

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

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)

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

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

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

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

Duration since history of HIV exposure, days Using 4th Generation (Ag-Ab combo) Enzyme Immunoassay to distinguish two groups of Fiebig I subjects Fiebig I subjects RNA+/p24-/3rd gen- (n=25) 4thG stage 1 4th gen- (n=18) 4thG stage 2 4th gen+ (n=7) P value HIV RNA, log10copies/ml 4.6 5.7 0.005 HIV DNA, copies/106 PBMC 7 312 0.002 Duration since history of HIV exposure, days 12.5 17 0.06 Ananworanich J, et al. Retrovirology 2013

Where we are now in RV254/ SEARCH 010 Goal 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?

RV254/SEARCH 010 Acknowledgement Thai Red Cross/Chula AFRIMS Volunteers Funding from US Military HIV Research Program MHRP Alexandra Schuetz Rapee Trichavaroj Vatcharain Assawadarachai Yuwadee Phuangngern Siriwat Akapirat Nantana Tantibul Panadda Sawangsinth Susan Mason Bessara Nuntapinit Wanwarang Khobchit Sakuna Suksawad Ajchariyarat Sangdara Kultida Poltavee Hathairat Savadsuk Suwittra Chaemchuen Surat Jongrakthaitae Chayada Sajiaweerawan Nipattra Tragonlugsana Putida Saetun Nelson Michael Jerome Kim Merlin Robb Hendrik Streeck Diane Bolton Bonnie Slike Sodsai Tovanabutra 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 Sukalya Lerdlum Supranee Buranapraditkun Duanghathai Suttichom Somprartthana Rattanamanee Peeraya Mangu Sasiwimol Ubolyam Mantana pothisri Phandee Wattanaboonyongcharoen Ponlapat Rojnuckarin Sopark Manasnayakorn Suteeraporn Pinyakorn 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 Thai GPO (TDF, 3TC, EFV, LPV/r) Gilead (TDF, FTC) Merck (EEV, RAL) Pfizer (MVC) Monogram (Trofile) VGTI Serena Spudich Idil Kore UMN Nicolas Chomont Claire Vandergeeten Rafick Sekaly Elias Haddad Lydie Trautmann Huntington Memorial Timothy Schacker Napaporn Sailasuta