1. Undetectable = Uninfectious ? Treatment as Prevention

2. AllMen-WomenWomen-Men « Rakai » Study: Transmission risk as a function of viral load No transmission if VL « undetectable » Quinn et al. N Engl J Med 2000;342:921-9

3. N Engl J Med 1999;341:394-402 Maternal levels of plasma HIV RNA and the risk of perinatal transmission No transmission if maternal viremia < 1000/ml Mother’s viremia of a non infected newborn Mother’s viremia of an infected newborn

4. Mother to Child Transmission AZT HAART % of infected children

5. Effect of HAART on MTCT 2202 babies born to HIV+ mothers with undetectable viral load at the time of confinement 3 neonatal infections Claire Townsend et al. 15th CROI, Poster 653

6. Transmission by breast milk % infected children IAS Conference Syndney, Abstracts TUAX 101 and 102 Mothers on NVP/3-TC/AZT, 2 studies in Kenya and Uganda, 441 and 172 pregnancies, one infection

7. Effects of HAART on heterosexual transmission Prospective studies of 393 heterosexual couples in Madrid The index patients were HIV positive, and consulted between 1991-2003 Partners’ only HIV risk was exposure to the index patients All partners had repeated HIV tests to investigate HIV infection in partners Castilla, et al. JAIDS 2005; 40:96-101

8. Prevalence of HIV infection in the partners Pre-HAARTHAART Pourcent des partenaires infecté(e)s

9. Castilla, et al. JAIDS 2005; 40:96-101 « HAART versus condoms » Infection rates in sex partners Ttmt of the index pt No ttmt Mono- ou bitherapy HAART Unsafe sex >1/month<1/moNever 0 2 4 6 8 10 12 0 1 2 3 4 5 6 7 8 9 10 % %

10. Condoms plus HAART in comparison to condoms alone: 2 African studies What they had in common: Transmission in Uganda Sero-discordant Couples Condom Promotion How they differed: Study A*, without HAART, evaluated the effect of circumcision on male-to-female transmission Study B**, with HAART, evaluated transmission both ways * Wawer M et al. Abstract 33 LB, 15th CROI, Boston 2008 **Bunnell R et al. Abstract 29, 15th CROI, Boston 2008

11. Results Study A*Study B** Condoms HAART- N infections observed12% ppy0.5 % ppy 95% CI9 – 150.01-3.0 * Wawer M et al. Abstract 33 LB, 15th CROI, Boston 2008 **Bunnell R et al. Abstract 29, 15th CROI, Boston 2008, AIDS 2006

12. Rwanda Follow-up of 1034 sero-discordant couples; in 248 the infected partner was on HAART In spite of condom promotion, 42 incident infections were observed HAARTNo HAART N total248786 Seroconversions240 Per cent0.85.1 * Kayitenkore K et al. 14th International AIDS Conference Toronto 2006, abstract no. MOKC101

13. In conclusion HAART lowers MTCT HAART lowers heterosexual transmission (no data on male homosexual transmission) In Africa and in Europe, HAART appears more efficacious than condoms, in sero- discordant heterosexual couples

14. Effects of HAART on the AIDS Epidemic Projections for British Columbia

15. Hogg et al. Unpublished, 2006 Treat all Treat 30% HIV infections per 1000 population 20061014182226303438422050

16. Costs of treatment Treat all Treat 30% 20061014182226303438422050 10 9 $ Hogg et al. Unpublished, 2006

17. Costs of HAART 20061014182226303438422050 Billions de $ Small investment Great savings Lima VD et al. Expanded Access to Highly Active Antiretroviral Therapy: A Powerful Strategy to Curb the HIV Epidemic; JID 2008; volume 198, July 1. Hogg et al. Unpublished, 2006

18. Next on the Agenda Controlled trials –In sero-discordant couples (HPTN 052 study already underway) –In the general population (planned) Important unsolved questions –Efficacy –Acceptability –Compliance –Sustainability

19. Undetectable = Uninfectious In Medicine, never say never… Biologically plausible Observational data with limits –Heterosexual couples –Low number = high upper limits of CIs How to position yourself when faced with small risks