who’s transmitting hiv? is it really the undiagnosed?

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…





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?

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

Recent Infection

Acute Infection

Chronic Infection

Unknown Infection


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

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10087

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10085

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96100

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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









n=1114

74% of transmitters are unknown or undiagnosed









n=1114









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?

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…



"We can't solve problems by using the same kind of thinking we used when we created them.”

Albert Einstein



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

who’s transmitting hiv? is it really the undiagnosed?

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health adviserswho