who’s transmitting hiv? is it really the undiagnosed?
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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…. - PowerPoint PPT PresentationTRANSCRIPT
Who’s transmitting HIV?Is it really the undiagnosed?
Dr David PaoLocum Consultant in GUM /HIVBrighton and Sussex University Hospitals, UK
Welcome to BrightonSea, sun and relax…
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Full of characters… 250,000 of them
Full of fun…
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Things fall apart…
The best laid plans of mice and men…
BrightonHIV cohort growth Drug Resistance (TDR):
HIV current cohort - patients seen within 1 year for HIV care
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Acute HCV infection - Brighton
2008 data projected from data to 11th March
Local data - BrightonDiagnosis 2007Chlamydia 904Gonorrhoea 309HIV infection (inc. transfers in) 214Syphilis (all stages) 125Acute HCV 23LGV 3
HIV vs. other STIs?
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Developing the Workforce, 2008 (DoH, SSHA, UNITE, NMC)
Health AdvisersWho are you?• 421 Health Advisers in 2007
– 336 nurses– 13 social workers– 67 counsellors– 46
psychologists/psychotherapists/teachers
Manual for Sexual Health Advisors 2004 (DoH, SSHA)
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)
SSHA ConferenceGlasgow 1998Workshops“Will Health Advising Survive Triple Combination Therapy?”
Par·a·digm n. 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.
Quinn et al, NEJM 2000;342:921-9
Sexual transmission risk and HIV viral load
Garcia PM, NEJM 1999
Prevention of mother-to-child transmission
No transmission if maternal viremia <
1000/ml
Vernazza P et al. Bulletin des Médecins Suisses 2008;89: No. 5
The Swiss StatementIndividual level
“HIV seropositive individuals on ART with afully suppressed viral load and no additional sexually transmitted infections do nottransmit HIV by sexual means.”Swiss Federal Commission for HIV / AIDSJanuary 2008
Granich RM et al. Lancet 2009; 373: 48-57
WHO Model 2009Population level
Test and Treat Concept“Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for eliminationof HIV transmission: a mathematical model.”WHO, Geneva Department of HIV/AIDSJanuary 2009
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…?
Where can we focus?
• Partner notification• Recent HIV infection• The undiagnosed• Future ideas
Moore ZS et al. JAIDS 2009
Partner notificationNorth Carolina 2002-2007
Recent HIVn=12050% partners tested9% partners +ve25% new +ve partners
recent
Chronic HIVn=904439% tested (p<.01)5% partners +ve
(p=.03)1% new +ve partners
recent (p<.01)
What about those who refuse HA intervention?
Determinants of HIV transmission: a longitudinal phylogenetic studyBrighton and Sussex University HospitalsUniversity College LondonHealth Protection Agency UK
Questions
How much do the following factors contribute to actual HIV transmissions in Brighton MSM?
• recent infection (seroconversion)• undiagnosed HIV infection • HAART• STIs
Recent Infection
Recent Infection
Acute Infection
Chronic Infection
Unknown Infection
Recent Infection So what?
HAART
No HAART
Recent Infection
Acute Infection
Acute Infection
Chronic Infection
Unknown Infection
Chronic Infection
HAART
No HAART
xRecent Infection So what?
Recent Infection
Recent Infection
Acute Infection
Chronic Infection
Recent Infection So what?
Recent Infection
Recent Infection
Acute Infection
Chronic Infection
Unknown Infection
Recent Infection So what?
Phylogenetics
Viral gene sequences
Phylogenetic tree
1 AAAGTTCTC…
2 AATGTTCTC…
3 AATGTTGTC…
2
1
3
Viral population
Infected population
1 2 31 2
3
Study of the origin, characteristics and spread of epidemics,based on viral diversity:
Pao D et al. AIDS AIDS 2005;19(1):85-90.
0.1 nucleotide substitutions per site
514
3411
33 7624
3510418
4793
6997
12 3613 22
2846101
6777
6496
7385 45
5558
9420
3132
57703979
5480
151778
8129
3071
744243
44102
DD
4865
9618
3768
5384
7249
8341
98103
86100
CC
7587
1016
212389
63EE
FF 2
33825 26
9546
4090 88
92509
19761
60B
B91
5166
5256
5982
6299
Outgroup K
100
100
10087
100
100
10085
100
100
100
100
100
100
100
100
97
10062
96100
100
100
100
100
10053
6198
6880
100
MethodsPhylogenetics
Results2000-2006
ResultsCohort Description 2000-2006
Recent HIVn=10 (24%)
Chronic HIVn=31 (76%)
Identified Most Likely Transmittern=41 (26%)
Recent HIV Infectionn=159 (19%)
Chronic HIV Infectionn=700 (81%)
pol Sequence Availablen=859 (75%)
HIV-1 MSM Cohort(2000 - 2006)
n=1114
ResultsCohort Description 2000-2006
Recent HIVn=10 (24%)
Chronic HIVn=31 (76%)
Identified Most Likely Transmittern=41 (26%)
Recent HIV Infectionn=159 (19%)
Chronic HIV Infectionn=700 (81%)
pol Sequence Availablen=859 (75%)
HIV-1 MSM Cohort(2000 - 2006)
n=1114
ResultsCohort Description 2000-2006
Recent HIVn=10 (24%)
Chronic HIVn=31 (76%)
Identified Most Likely Transmittern=41 (26%)
Recent HIV Infectionn=159 (19%)
Chronic HIV Infectionn=700 (81%)
pol Sequence Availablen=859 (75%)
HIV-1 MSM Cohort(2000 - 2006)
n=1114
74% of transmitters are unknown or undiagnosed
ResultsCohort Description 2000-2006
Recent HIVn=10 (24%)
Chronic HIVn=31 (76%)
Identified Most Likely Transmittern=41 (26%)
Recent HIV Infectionn=159 (19%)
Chronic HIV Infectionn=700 (81%)
pol Sequence Availablen=859 (75%)
HIV-1 MSM Cohort(2000 - 2006)
n=1114
ResultsCohort Description 2000-2006
Recent HIVn=10 (24%)
Chronic HIVn=31 (76%)
Identified Most Likely Transmittern=41 (26%)
Recent HIV Infectionn=159 (19%)
Chronic HIV Infectionn=700 (81%)
pol Sequence Availablen=859 (75%)
HIV-1 MSM Cohort(2000 - 2006)
n=1114
recent infection: 2% of follow-up time but 24% of transmissions
Results3 major outcomes1. 74% of transmissions most likely come
from undiagnosed HIV
2. Effect of recent infection– 2% of follow-up time but 24% of
transmissions
3. What else can we do?
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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
ResultsFactors associated with transmission (Univariate*)
Factor Rate Ratio
95% CI p-value
Viral Load (per log10 increase)
2.38 1.82 - 3.11
0.0001
Recent Infection 4.03 1.88 - 8.68
0.0004
STI during interval 12.53 6.13 - 25.64
0.0001
Age (per 5 years older) 0.51 0.41 - 0.65
0.0001
On HAART 0.04 0.01 - 0.19
0.0001*Poisson Regression ModelNo association with CD4 count, AIDS diagnoses or calendar year of diagnosis
ResultsFactors associated with transmission (Multivariate*)
Factor Rate Ratio
95% CI p-value
Viral Load (per log10 increase)
1.68 1.19 - 2.36
0.003
Recent Infection 3.43 1.52 - 7.73
0.003
STI during interval 5.64 2.65 - 12.02
0.0001
Age (per 5 years older) 0.68 0.54 - 0.85
0.0009
On HAART 0.28 0.05 - 1.44
0.13*Poisson Regression Model - variables in model include calendar year as well as those above
(based on math. Model by Wilson et al.)
Garnett &Gazzard, The Lancet, 27.7.2008, editorialcomment
In serodiscordant male coupleafter 100 anal contacts
Swiss statement challengedconfir
med
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
“We don’t know what it is, but we do know it’s contagious”
A shift from The Good Old Days…
To a (truly) new paradigm…
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"We can't solve problems by using the same kind of thinking we used when we created them.”
Albert Einstein
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HAPPEN
Thank you for listening
and
Enjoy your conference!
AcknowledgementsBrighton and Sussex University HospitalsMartin 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, LondonDeenan Pillay, Caroline Sabin, Noel Gill
Health Protection Agency, Colindale, London, UKJohn Parry, Alison Brown, Gary Murphy, Andrew Buckton, Pat Cane