Treatment as Prevention (TasP)

Dr Michael BradyMedical Director, Terrence Higgins Trust

Consultant, HIV & Sexual Health

Reducing onward transmission: Viral suppression among key population groups living with HIV in the United Kingdom. 19th Annual Conference of the British HIV Association (BHIVA) April 2013, Valerie Delpech, Alison Brown, Stephano Conti, Venkata Polavarapu, Zing Yin

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Efficacy0% 10 20 30 40 50 60 70 80 90 100%

Effect size (95% CI)

Tenofovir/Truvada for discordant couples 73% (49; 85)

Study

Medical male circumcision 54% (38; 66)

Prime boost Vaccine 31% (1; 51)39% (6; 60)Tenofovir vaginal

(coital)

Truvada for MSMs 44% (15; 63)

96% (73; 99)Treatment for prevention

Truvada for heterosexuals 63% (22; 83)

Truvada for women 0% (-69; 41)

Tenofovir gel (daily)for women

15% (-20; 40)Truvada for women 0% (-50; 30)

Stable, healthy, serodiscordant couples, sexually activeCD4 count: 350 to 550 cells/mm3

Primary Transmission EndpointVirologically-linked transmission events

Primary Clinical EndpointWHO stage 4 clinical events, pulmonary tuberculosis, severe

bacterial infection and/or death

HPTN 052 Study Design

Immediate ART CD4 350-550

Delayed ART CD4 <250

Randomization

Total HIV-1 Transmission Events: 39

HPTN 052: HIV-1 Transmission

Linked Transmissions: 28

Unlinked or TBD Transmissions: 11

p < 0.001

Immediate Arm: 1

Delayed Arm: 27

• 18/28 (64%) transmissions from infected participants with CD4 >350 cells/mm3

• 23/28 (82%) transmissions in sub-Saharan Africa

• 18/28 (64%) transmissions from female to male partners

96% reduction in HIV Transmission

HIV Treatment GuidelinesGuideline Recommended CD4 at start of therapy

WHO (2013) < 500

BHIVA (2013) < 350Respect decision if patient wants to

start to reduce transmission

DHHS - USA (2012) All irrespective of CD4 count

IAS (2012) All irrespective of CD4 count

EACS (2013) <350Consider 350 – 500 and >500

Reducing onward transmission: Viral suppression among key population groups living with HIV in the United Kingdom. 19th Annual Conference of the British HIV Association (BHIVA) April 2013, Valerie Delpech, Alison Brown, Stephano Conti, Venkata Polavarapu, Zing Yin

Distribution of viral load among gay men living with HIV in the UK in 2010

HIV treatment as prevention among men who have sex with men in the UK: is transmission controlled by universal access to HIV treatment and care?AE Brown*,ON Gill, VC Delpech, Article first published online: 28 July 2013, HIV Medicine, Volume 14, Issue 9, pages 563–570, October 2013

What is the potential impact of starting treatment early?

• ART started at CD4 <500 could have reduced the proportion of PLWHIV with detectable viraemia from 42% to 38%

• Halving the undiagnosed population could have led to to a decrease to 28%

“Unlikely early treatment will reduce HIV transmission unless undiagnosed population is

substantially reduced”Brown et al AIDS 2014 Jan 14;28(2):281-3

What is the potential impact of starting treatment early?

• Extending ART to all diagnosed HIV infected MSM with CD4 <500 in 2010 would reduce proportion of infectious men from 35% – 29%.

• Halving the proportion who are undiagnosed would further reduce this to 21%

“The effectiveness of treatment as prevention will be limited unless the undiagnosed population is reduced through frequent HIV testing and consistent condom

use”

Brown et al AIDS 2014 Jan 14;28(2):281-3

Can we afford it?

• Estimated annual population treatment and care costs:– £104 million in 1997– £483 million in 2006– £721 million in 2013

Mandalia et al PLoS One 2010; 5:e15677

Summary: TasP

• The best evidence for effectiveness of an intervention to reduce transmission

• Effectiveness depends on knowing HIV status and therefore interlinked with testing strategies

• Cost may prohibitive

With limited resources do we

focus on:

ART for HIV positive people?

ART for HIV negative people?

Reduced transmission?cost

?adherence?sexual behaviour

?other STIs

Reduced transmissionReduced morbidityReduced mortality

Better quality of lifeLow pill burden

Low toxicity