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Undetectable = Uninfectious ?

Undetectable = Uninfectious ?. Treatment as Prevention. All Men-Women Women-Men. No transmission if VL « undetectable ». « Rakai » Study: Transmission risk as a function of viral load. Quinn et al. N Engl J Med 2000;342:921-9. N Engl J Med 1999;341:394-402

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Undetectable = Uninfectious ?

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  1. Undetectable = Uninfectious ? Treatment as Prevention

  2. All Men-Women Women-Men No transmission if VL « undetectable » « Rakai » Study: Transmission risk as a function of viral load 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 • Mother’s viremia of a non infected newborn • Mother’s viremia of an infected newborn No transmission if maternal viremia < 1000/ml

  4. Mother to Child Transmission AZT HAART % ofinfected 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 Mothers on NVP/3-TC/AZT, 2 studies in Kenya and Uganda, 441 and 172 pregnancies, one infection % infected children IAS Conference Syndney, Abstracts TUAX 101 and 102

  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-HAART HAART Pourcent des partenaires infecté(e)s

  9. « HAART versus condoms »Infection rates in sex partners Unsafe sex Ttmt of the index pt No ttmt Mono- oubitherapy >1/month <1/mo Never HAART % % 12 10 9 10 8 8 7 6 6 5 4 4 3 2 2 1 0 0 Castilla, et al. JAIDS 2005; 40:96-101

  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 observed 12% ppy 0.5 % ppy 95% CI 9 – 15 0.01-3.0 * 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 HAART No HAART N total 248 786 Seroconversions 2 40 Per cent 0.8 5.1 * Kayitenkore K et al. 14th International AIDS ConferenceToronto 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. 10 9 8 7 6 5 4 3 2 1 0 2006 2010 2014 2018 2022 2026 2030 2034 2038 Treat 30% HIV infections per 1000 population Treat all 2006 10 14 18 22 26 30 34 38 42 2050 Hogg et al. Unpublished, 2006

  16. Costs of treatment 109 $ Treat all Treat 30% 2006 10 14 18 22 26 30 34 38 42 2050 Hogg et al. Unpublished, 2006

  17. Costs of HAART Billions de $ Great savings Small investment 2006 10 14 18 22 26 30 34 38 42 2050 • 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

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