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Treatment of HIV Stops Transmission : Where DO We Go From Here? Cohen et al Lancet , Nov. 2013

Treatment of HIV Stops Transmission : Where DO We Go From Here? Cohen et al Lancet , Nov. 2013. Myron S. Cohen, MD Yergan-Bate Professor Medicine, Microbiology and Epidemiology Director, Institute for Global Health & Infectious Diseases. BACK TO BASICS How HIV Became Pandemic. Ro = bDC

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Treatment of HIV Stops Transmission : Where DO We Go From Here? Cohen et al Lancet , Nov. 2013

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  1. Treatment of HIV Stops Transmission: Where DO We Go From Here?Cohen et al Lancet , Nov. 2013 Myron S. Cohen, MD Yergan-Bate Professor Medicine, Microbiology and Epidemiology Director, Institute for Global Health & Infectious Diseases

  2. BACK TO BASICSHow HIV Became Pandemic Ro = bDC When Ro >1 epidemic is sustained b = Efficiency of transmission D = Duration of infectiousness C = Number of people (partners) exposed Anderson and May, 1966

  3. Viral Load Predicts Heterosexual Transmission Source: Quinn et al. (2000). N Engl J Med, 342, 13, 921–929.

  4. EXPOSED UNEXPOSED EXPOSED (precoital/coital) (postcoital) Behavioral, Structural Vaccines ART PrEP Microbicides Vaccines ART PEP Structural Circumcision Condoms YEARS HOURS 72h Four Prevention OpportunitiesCohen et al. Lancet, 2013 INFECTED Treatment Of HIVReduced Infectivity YEARS

  5. AIDS 24:621, 2010

  6. EXPOSED UNEXPOSED EXPOSED (precoital/coital) (postcoital) Behavioral, Structural Vaccines ART PrEP Microbicides Vaccines ART PEP Structural Circumcision Condoms YEARS HOURS 72h Four Prevention OpportunitiesCohen et al. Lancet, 2013 INFECTED Treatment Of HIVReduced Infectivity YEARS

  7. Antiretroviral Exposure at Mucosal Surfaces Rectal Tissue, CVF, Semen Exposure Relative to Blood CCR5 Receptor Antagonists Integrase Inhibitors Nonnucleoside RT Inhibitors Nucleoside(tide) RT Inhibitors Protease Inhibitors RAL (150) TFV (46) MRV (27) RTV (13) 3TC (6) ETR (8) TFV (5) FTC/ 3TC (4) MRV (4) D4T (3.5) DRV (2.7) FTC (2.6) RAL (2) ZDV (2) ZDV (2) ETR (1.3) IDV (2) ABC (1.5) IDV (1) TFV (1) NVP (0.8) RAL (1) NVP (0.7) MRV (0.6) APV (0.5) EVF (0.6) DDI (0.21) RTV (0.3) APV (0.2) DLV (0.2) ATV (0.18) DRV (0.17) ETR (0.15) ABC (0.08) LPV (0.08) D4T (0.05) LPV/NFV (0.05) EFV (0.03) SQV & RTV (0.03) SQV (ND) RECTAL TISSUE CERVICOVAGINAL FLUID SEMEN

  8. HPTN 052 Enrollment Cohen et al NEJM, July 2011 U.S. Thailand India Americas 278 Kenya Malawi Asia 531 Brazil Zimbabwe Botswana South Africa Africa 954

  9. “The results have galvanized efforts to end the world’s AIDS epidemic in a way that would have been inconceivable even a year ago” Bruce Alberts, editor of Science

  10. The Economist, June 2011

  11. Risk Comparison of Serodiscordant Couples Anglemeyer et al. JAMA 2013

  12. HPTN 052: Primary EndpointsGrinsztejn et al Lancet ID (in press)

  13. HIV-1 RNA and CD4 Over Time (ITT) Grinstejn et al. Lancet ID (in press) Immediate CD4 (cells/mm3) Delayed Proportion <400 copies/ml Immediate Delayed

  14. COHERE Study 1998-2010 Relationship between current CD4 and AIDS-defining illness with a CD4 count ≥500 cells/μL: relationship with current viral load and antiretroviral treatment First 6 mo cART All patients ARV naive VL < 400 VL > 400 A. Mocroft, et al., Oxford Journal, August 2013

  15. EVERYONE Should Start ARTIAS-USA DHHS Guidelines • HIV replication has negative consequences • Earlier ART prolongs survival • ART blocks HIV transmission BUT… arguments for delay in ART include • Anticipated detection of novel “harm” (?) • Ongoing search for visible “benefit” (?) • START and TEMPERANO studies (?) • Distracting focus on logistical challenges

  16. HPTN 052 Cost EffectivenessWalensky et al. NEJM, 2013 HPTN 052 results for India, South Africa used Treatment/Prevention benefits both considered i) In South Africa, over the short term, early ART is “cost-saving” ii) Over time ART in INDIA and South Africa proves “very cost effective”

  17. Higher employment at CD4≥500 Thurminathy, Health Affairs ,2012 • Compared to CD4<200, CD4≥500 associated with • 5.8 more days/month • 2.2 more hours/day (40% more than ref. mean of 5.5) • Linear regression model with age, age-squared, and sex included as controls • ** p<0.05, * p<0.10 • Reference group has CD4<200 Those with CD4≥500 worked nearly 1 week/month more than those with CD4<200, and as much as HIV-uninfected adults

  18. Who SHOULD We Treat? • Couples (WHO Guidelines) • CD4 Count>500 (WHO) • Pregnant women (WHO) WHO estimates 26,000,00 people

  19. Fig. 1a: Time series of maps showing the evolution of the proportion of the HIV-infected adults (≥15 years of age) receiving ART across the demographic surveillance area (2005 to 2008, left to right, top row; 2009 to 2011, left to right, bottom row). F Tanser et al. Science 2013;339:966-971

  20. Antiretroviral Treatment Prevents HIV • Axiom: viral suppression stops HIV spread • Axiom: immediate ART improves health • 30 years of “mixed messages” are a problem • A NEW message will improve adherence • Immediate, universal ART is the best strategy available for the HIV pandemic

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