Acute HIV infection detection and control reduces HIV infectiousness and transmission risk behavior among men who have

1. Acute HIV infection detection and control reduces HIV infectiousness and transmission risk behavior among men who have sex with men in Bangkok, Thailand Frits van Griensven, Nittaya Phanuphak, Eugène Kroon, James Fletcher, Suteera Pinyakorn, Nitiya Chomchey, Siriwat Akapirat, Rapee Trichavaroj, Mark de Souza, Jerome Kim, and Jintanat Ananworanich, on behalf of the RV254/SEARCH 010 Study Group

2. Background • Antiretroviral treatment (ART) reduces HIV viral load and HIV transmission in HIV discordant heterosexual couples1 and likely MSM2 • Despite increased uptake of ART since 1996, HIV incidence in MSM continues on a global level3 • In rising and ongoing HIV epidemics in MSM, such as in Bangkok, most HIV transmission may occur prior to ART initiation4 • Newly HIV infected MSM in Bangkok are mostly young men in a multi risk factor environment, which includes unidentified acute and newly HIV infected other MSM5 • Phylogenetic clustering of new HIV infections in MSM supports acute HIV infection as one of the main drivers of ongoing HIV transmission in MSM in rising and ongoing HIV epidemics4,6,7 1Cohen et al. N Engl J Med 2011;365:493-505 (HPTN052); 2Porco et al. AIDS 2004;18:81-88; 3Beyrer et al. Lancet 2012;380:367-77; 4 Fisher et al. AIDS 2010; 24(11):1739-47; 5van Griensven et al. AIDS2013;27(5):825-32; 6Audelin et al. J Acquir Immune DeficSyndr2013;62(1):102-8; 7Ye J, et al. PLoS ONE 2013;8(1): e54238. doi:10.1371/journal.pone.0054238

3. RV254/SEARCH010 Study A cohort of individuals in acute HIV infection (AHI) in Bangkok, Thailand Purpose: Describe clinical, immunological, and virologicalcharacteristics during AHI for vaccine development and (functional) HIV cure insights Describe demographics and behavioral risk factors for those identified with acute HIV infection Intervention: Immediate initiation of ART upon detection of AHI Behavioral risk reduction counseling Outcomes: Markers of HIV disease progression or cure Behavioral change

4. RV254/SEARCH010 Study Screening EIA/NAT 69,911 samples 136 AHI identified April 2009-March 2013 90 MSM in AHI identified screening3 days 2 days after study entry 88 MSM started ART 90% undetectable integrated HIV-DNA in PBMC at 1 year Candidates for functional cure research 36 not included in study 10 non-MSM To bereported elsewhere Here we look at reduction in HIV VL and transmission risk behavior to assess possible impact of AHI control on epidemic spread

7. Blood plasma viral load

8. Seminal plasma viral load Beyond week 2: If blood plasma VL < detection, also seminal plasma VL < detection

9. Anal lavage viral load

10. Reported number of sexual partners All wk 24 and wk 48 changes from baseline p<0.05 Changes from wk 24 to wk 48 NS

11. Unprotected intercourse over preceding 4 months wk 24 and wk 48 vs wk 0 p< 0.0001 wk 48 vs wk 24 NS

12. What is next? Estimating the number of transmissions averted through ART and behavioral change in AHI David Wilson and colleagues Kirby Institute University of New South Wales

14. Discussion • Initiation of ART during AHI may be a promising intervention towards establishing functional HIV cure • Sharp and rapid decreases in HIV blood plasma VL and seminal plasma VL are seen, which translate into potent HIV transmission reduction • Impressive behavioral changes during the early stages after AHI diagnosis, ART initiation and risk reduction counseling • Impact of early ART during AHI on transmission likely depends on the HIV epidemic stage; literature puts HIV transmissions resulting from AHI partners anywhere from 4% to 50%1,2 1Goodreau et al. PLoS ONE 2012;7(11): e50522; 2Brenner et al. J Infect Dis 2007;195:951-9

15. Discussion (cont.) • Seminal VL peaks at 30 days post infection in untreated subjects3 while in this cohort immediate decline was seen on ART and 73% VL < detection at week 4 • Near 100% undetectable VL in seminal plasma at weeks 12 and 24 plus 100% correlation with blood plasma VL This contrasts with seminal plasma VL studies in North American MSM with undetectable blood plasma VL on ART4,5 3Pilcher et al. AIDS 2007;21:1723-30 4Politch et al. AIDS 2012;26:1535-43 5Sheth et al. AIDS 2009;23:2050-4

16. Conclusion • Early ART greatly reduces infectiousness in AHI • Impressive changes in risk behavior after ART and risk reduction counseling initiation, sustained up to 48 weeks • AHI detection and control may be a powerful HIV prevention measure in rising and ongoing HIV epidemics in MSM

17. Acknowledgements the RV254/SEARCH010 study volunteers Funding from US Military HIV Research Program AFRIMS Thai Red Cross/Chula Kirby o David Wilson o Lei Zhang o Andrew Shattock o Praphan Phanuphak o Thep Chalermchai o Nipat Teeratakulpisarn o RungsunRerknimitr o WiriyapornRidtitid o SukalyaLerdlum o Alexandra Schuetz o Vatcharain Assawadarachai o Yuwadee Phuangngern o Wiriya Rutvisuttinunt o Nantana Tantibul o Panadda Sawangsinth o Bessara Nuntapinit o Wanwarang Khobchit o Sakuna Suksawad NIAID o IriniSereti o Daniel Douek o Netanya Sandler o Mary Marovich o Duanghathai Suttichom o Somprartthana Rattanamanee o Peeraya Mangu o Sasiwimol Ubolyam o MantanaPothisri NCI o Ajchariyarat Sangdara o Kultida Poltavee o HathairatSavadsuk o Suwittra Chaemchuen o Robert Paris o SuratJongrakthaitae o Chayada Sajiaweerawan o NipattraTragonlugsana o PutidaSaetun o Jacob Estes o Robin Dewar o Adam Rupert WRAIR SAIC-Frederick o Bonnie Slike o SodsaiTovanabutra o Gustavo Kijak o Frank Maldarelli o Mary Kearney o Ann Wiggins Industry Huntington Memorial UCSF o NapapornSailasuta o Thai GPO (TDF, 3TC, EFV, LPV/r) o Gilead (TDF, FTC) o Merck (EEV, RAL) o Pfizer (MVC) o Monogram (Trofile) o Victor Valcour VGTI Yale o Elias Haddad o LydieTrautmann o Serena Spudich o IdilKore