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Who’s transmitting HIV? Is it really the undiagnosed?

Who’s transmitting HIV? Is it really the undiagnosed?. Dr David Pao Locum Consultant in GUM /HIV Brighton and Sussex University Hospitals, UK. Welcome to Brighton Sea, sun and relax…. Full of characters… 250,000 of them. Full of fun…. Things fall apart….

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Who’s transmitting HIV? Is it really the undiagnosed?

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  1. Who’s transmitting HIV?Is it really the undiagnosed? Dr David Pao Locum Consultant in GUM /HIV Brighton and Sussex University Hospitals, UK

  2. Welcome to BrightonSea, sun and relax…

  3. Full of characters… 250,000 of them

  4. Full of fun…

  5. Things fall apart…

  6. The best laid plans of mice and men…

  7. BrightonHIV cohort growth Drug Resistance (TDR):

  8. Acute HCV infection - Brighton 2008 data projected from data to 11th March

  9. Local data - Brighton HIV vs. other STIs?

  10. Health AdvisersWho are you? • 421 Health Advisers in 2007 • 336 nurses • 13 social workers • 67 counsellors • 46 psychologists/psychotherapists/teachers Developing the Workforce, 2008 (DoH, SSHA, UNITE, NMC)

  11. Health AdvisersRemit • Partner notification / contact tracing • Sexual health promotion • Teaching / training • Counselling • Research and audit “Partner notification… has been demonstrated to be an effective aspect of managing sexually transmitted infection.” (Payne & O’Brien 2005; NICE 2007) Manual for Sexual Health Advisors 2004 (DoH, SSHA)

  12. SSHA Conference Glasgow 1998 Workshops “Will Health Advising Survive Triple Combination Therapy?” Par·a·digmn. A set of assumptions, concepts, values, and practices that constitutes a way of viewing reality for the community that shares them, especially in an intellectual discipline.

  13. Sexual transmission risk and HIV viral load Quinn et al, NEJM 2000;342:921-9

  14. Prevention of mother-to-child transmission No transmission if maternal viremia < 1000/ml Garcia PM, NEJM 1999

  15. The Swiss StatementIndividual level “HIV seropositive individuals on ART with a fully suppressed viral load and no additional sexually transmitted infections do not transmit HIV by sexual means.” Swiss Federal Commission for HIV / AIDS January 2008 Vernazza P et al. Bulletin des Médecins Suisses 2008;89: No. 5

  16. WHOModel 2009Population level Test and Treat Concept “Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model.” WHO, Geneva Department of HIV/AIDS January 2009 Granich RM et al. Lancet 2009; 373: 48-57

  17. WHO Model 2009Conclusions • Universal testing and treatment would reduce new HIV cases by 95% by 2020 • Limitations: adherence, change of behaviour, resistance, toxicity, financing • What about in the real world…?

  18. Where can we focus? • Partner notification • Recent HIV infection • The undiagnosed • Future ideas

  19. Partner notificationNorth Carolina 2002-2007 Recent HIV n=120 50% partners tested 9% partners +ve 25% new +ve partners recent Chronic HIV n=9044 39% tested (p<.01) 5% partners +ve (p=.03) 1% new +ve partners recent (p<.01) What about those who refuse HA intervention? Moore ZS et al. JAIDS 2009

  20. Determinants of HIV transmission: a longitudinal phylogenetic studyBrighton and Sussex University HospitalsUniversity College LondonHealth Protection Agency UK

  21. Questions How much do the following factors contribute to actual HIV transmissions in Brighton MSM? • recent infection (seroconversion) • undiagnosed HIV infection • HAART • STIs

  22. Recent Infection So what? Recent Infection Recent Infection Chronic Infection HAART No HAART Unknown Infection Acute Infection

  23. Recent Infection So what? Acute Infection x Chronic Infection HAART Recent Infection No HAART Chronic Infection Unknown Infection Acute Infection

  24. Recent Infection So what? Recent Infection Recent Infection Chronic Infection Acute Infection

  25. Recent Infection So what? Recent Infection Recent Infection Chronic Infection Unknown Infection Acute Infection

  26. 2 3 1 1 2 1 AAAGTTCTC… 2 AATGTTCTC… 3 AATGTTGTC… 1 2 3 3 Infected population Viral population Viral gene sequences Phylogenetic tree Phylogenetics • Study of the origin, characteristics and spread of epidemics, • based on viral diversity:

  27. 5 14 34 100 11 33 76 100 24 MethodsPhylogenetics 35 104 100 1 8 47 93 69 97 100 12 36 100 13 22 28 46 101 97 67 77 64 96 73 85 45 55 58 94 20 96 100 31 32 57 70 39 79 54 80 100 15 17 78 81 100 29 62 30 71 74 42 43 44 102 100 D D 48 65 96 100 18 37 68 53 84 72 49 83 41 98 103 86 100 100 C C 75 87 100 10 16 100 21 89 23 63 100 E E 100 F 87 F 2 100 3 38 100 25 26 95 100 4 6 40 88 90 92 50 85 9 100 19 7 61 60 100 B B 91 100 51 Pao D et al. AIDS AIDS 2005;19(1):85-90. 53 66 100 52 61 56 98 59 68 82 80 62 99 0.1 nucleotide substitutions per site Outgroup K

  28. Results2000-2006

  29. ResultsCohort Description 2000-2006

  30. ResultsCohort Description 2000-2006

  31. ResultsCohort Description 2000-2006 74% of transmitters are unknown or undiagnosed

  32. ResultsCohort Description 2000-2006

  33. ResultsCohort Description 2000-2006 recent infection: 2% of follow-up time but 24% of transmissions

  34. Results3 major outcomes • 74% of transmissions most likely come from undiagnosed HIV • Effect of recent infection • 2% of follow-up time but 24% of transmissions • What else can we do?

  35. BHIVA guidance Urge all healthcare workers to consider HIV testing in a wide range of situations and settiges of late and undiagnosed HIV For high HIV prevalent areas >2/1000 Clinical Indicator Diseases Antenatal testing

  36. ResultsFactors associated with transmission (Univariate*) *Poisson Regression Model No association with CD4 count, AIDS diagnoses or calendar year of diagnosis

  37. ResultsFactors associated with transmission (Multivariate*) *Poisson Regression Model - variables in model include calendar year as well as those above

  38. (based on math. Model by Wilson et al.) Swiss statement challenged confirmed In serodiscordant male couple after 100 anal contacts Garnett &Gazzard, The Lancet, 27.7.2008, editorialcomment

  39. What else can we do? • Partner notification - better targeting (multi-disciplinary) • Motivational interviewing and beyond • More sophisticated behavioural research • Build the evidence base for HA intervention

  40. A shift from The Good Old Days… “We don’t know what it is, but we do know it’s contagious”

  41. To a (truly) new paradigm… "We can't solve problems by using the same kind of thinking we used when we created them.” Albert Einstein

  42. Thank you for listening and Enjoy your conference! HAPPEN

  43. Acknowledgements Brighton and Sussex University Hospitals Martin Fisher, Gill Dean, Kate Nambiar, Stuart Tilbury, Denis McElborough, Gary Homer, Darshan Sudarshi, staff and patients of the Lawson Unit University College and Royal Free Hospitals Medical School, London Deenan Pillay, Caroline Sabin, Noel Gill Health Protection Agency, Colindale, London, UK John Parry, Alison Brown, Gary Murphy, Andrew Buckton, Pat Cane

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