Early treatment initiation: RV254/SEARCH 010 Study Group Jintanat Ananworanich on behalf of the RV254/SEARCH 010 Study Group [email protected].

Early treatment initiation: RV254/SEARCH 010

Study Group

Jintanat Ananworanich on behalf of the RV254/SEARCH 010 Study Group

[email protected]

Characteristics (n=100) ValuesMedian 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 logCRF_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 HIVhad undetectable integrated HIV DNA

after one year of antiretroviral treatment

100% 89%

Integrated HIV DNA at time of acute HIV infection

Fiebig III

Fiebig I

Not detected Not detectedNot

detected

Ananworanich J, et al. 2013 CROI (abstract 47)

Fiebig I

Integrated HIV DNA at 24 weeks after ART

Not detected

Chronic HIV

Not detected

Fiebig III

MegaHAART vs. HAART

Total HIV DNA

Integrated HIV DNA 2 LTR circles

Randomization (24 wks)

TDF + 3TC/FTC + EFV + RAL + MVCvs.

TDF + 3TC/FTC + EFV

Followed byTDF + 3TC/FTC + EFV

Half of Fiebig I subjects have non-reactive2nd generation EIA and/or Western Blot

at 24 weeks after ART

Non-reactive 2nd generation EIA Non-reactive/IND Western Blot

CD4/CD8 ratio ≥ 1Wk 0: 88% in Fiebig I vs. 20% in Fiebig III, p < 0.001Wk 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

Number of responders

4/30 (13%)

11/17 (65%)

CD8

6/30(20%)

2/17(12%)

CD4

Using 4th Generation (Ag-Ab combo) Enzyme Immunoassay to distinguish

two groups of Fiebig I subjects

Fiebig I subjectsRNA+/p24-/3rd

gen- (n=25)

4thG stage 14th 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, days12.5 17 0.06

Ananworanich J, et al. Retrovirology 2013

Where we are now

in RV254/SEARCH 010ART initiated

during acute HIV

restricted infection in PBMCs and TCM

Hypothesis 1Is early ART alone sufficient to cure in patients treated

during Fiebig I?

Hypothesis 2Will therapeutic HIV vaccine

+ early ART result in better viremic control vs. early ART alone?

GoalFunctional cure(Viremic control

without ART)

Hypothesis 3Will HDACi + early ART result in

depletion of reservoir/cure vs. early ART alone?

Hypothesis 4Will anti-inflammatory drugs +

early ART result in less immune activation and reservoir

vs. early ART alone?

A series of randomized trials are being developed

RV254/SEARCH 010 Acknowledgement

AFRIMSo Alexandra Schuetzo Rapee Trichavarojo Vatcharain Assawadarachaio Yuwadee Phuangngerno Rapee Trichavarojo Siriwat Akapirato Nantana Tantibulo Panadda Sawangsintho Susan Masono Bessara Nuntapinito Wanwarang Khobchito Sakuna Suksawado Ajchariyarat Sangdarao Kultida Poltaveeo Hathairat Savadsuko Suwittra Chaemchueno Surat Jongrakthaitae o Chayada Sajiaweerawan o Nipattra Tragonlugsana   o Putida  Saetun

o Thai GPO (TDF, 3TC, EFV, LPV/r)o Gilead (TDF, FTC)o Merck (EEV, RAL)o Pfizer (MVC)o Monogram (Trofile)

Thai Red Cross/ChulaMHRP

SAIC-Frederick

o Irini Seretio Daniel Doueko Netanya Sandlero Mary Marovich

Industry

Huntington Memorial

o Victor ValcourUCSF

o Praphan Phanuphako Kiat Ruxrungthamo Mark de Souzao Frits van Griensveno Thep Chalermchaio James LK Fletchero Eugene Kroono Nipat Teeratakulpisarno Rungsun Rerknimitro Wiriyaporn Ridtitid o Sukalya Lerdlumo Supranee Buranapraditkuno Duanghathai Suttichomo Somprartthana Rattanamaneeo Peeraya Manguo Sasiwimol Ubolyamo Mantana pothisrio Phandee

Wattanaboonyongcharoeno Ponlapat Rojnuckarino Sopark Manasnayakorno Suteeraporn Pinyakorn

o Nelson Michaelo Jerome Kimo Merlin Robbo Hendrik Streecko Diane Boltono Bonnie Slikeo Sodsai Tovanabutrao Gustavo Kijako Jean-Louis Excler

VGTIo Nicolas Chomonto Claire Vandergeeteno Rafick Sekalyo Elias Haddado Lydie Trautmanno Napaporn Sailasuta

o Frank Maldarellio Mary Kearneyo Ann Wiggins

NCIo Jacob Esteso Robin Dewaro Adam Rupert

NIAID

Yaleo Serena Spudicho Idil Kore

Volunteers Funding from US Military HIV Research Program

UMNo Timothy Schacker