1. Research to design community based prevention IAS Satellite – July 17, 2011 “Controlling the HIV epidemic – The promise of ARV-based prevention”

2. FB Infektiologie / Spitalhygiene Planning community based interventions The trivial key questions When does infection occur Where does it occur Who is most likely to transmit HIV Who is most likely to get infected What is the impact of behavior

3. FB Infektiologie / Spitalhygiene Who is most likely to transmit HIV Blood and Genital Viral Load 0 10 20 30 <400400- 3500 3500- 10'000 10'000- 50'000 >50000 Blood HIV-RNA (cp/ml) % partners infected Beaten, Science Trsl Medicine 2011 Semen HIV-RNA (cp/ml) Quinn, NEJM, 2000; 342:921-9

4. FB Infektiologie / Spitalhygiene Infectiousness (arbritrary scale) Months / Years Weeks PHI STDs When does HIV transmission occur? The role of PHI and STDs Vernazza et al, AIDS, 1999

5. FB Infektiologie / Spitalhygiene Pilcher et al JID 2004; 189:1785–92 Weeks after infection 20161814121086420 0.05 0.04 0.03 0.02 0.01 0.00 Transmission risk per sexual act When does HIV transmission occur? The role of Primary HIV Infection

6. FB Infektiologie / Spitalhygiene When does HIV transmission occur? The role of Primary HIV Infection  30% of PHI in clusters Yerly, AIDS 2001 Brenner, JID 2007 > 50% PHI clustered

7. FB Infektiologie / Spitalhygiene Pilcher et al, AIDS, 20.8.2007; 21:1723–1730 7 PHI: Long duration of infectivity n = 16 PHI with neg WB Malawi 17 d 30 d Blood Semen

8. FB Infektiologie / Spitalhygiene Bottleneck of Transmission

9. FB Infektiologie / Spitalhygiene Not all viruses are transmitted equally Immune system Founder virus unchanged Redd, CROI 2011 ♯ 160 / Wilen, J Virol 2011 / Nawaz, PLoS Pathogen 2011

10. FB Infektiologie / Spitalhygiene Who is getting infected ? HIV infections are clustered (Clade B) 5700 Patients, >50% in 60 Clusters Define: –Swiss clusters: Different from Intl sequ. –MSM or IDU/Het-clusters: 80% Kouyos et al, 2010 JID

11. FB Infektiologie / Spitalhygiene HIV infections in Switzerland are clustered HIV-epidemic in HET not sustained Kouyos et al, 2010 JID Clustering of HIV sequences in heterosexual acquisition

12. FB Infektiologie / Spitalhygiene Wolf et al, AIDS 2003

13. FB Infektiologie / Spitalhygiene Conclusions The first few months of HIV infection may be major driver of the epidemic In Switzerland, the HIV epidemic is primarily maintained in MSM (at least clade B)