What do models estimate to be the impacts on HIV incidence of various percentages of people with HIV...
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Transcript of What do models estimate to be the impacts on HIV incidence of various percentages of people with HIV...
What do models estimate to be the impacts on HIV incidence of various percentages of people with HIV on ART ?
National AIDS TrustTreatment as Prevention Seminar25th November 2010Southwark Cathedral, London
Death rate ~ 5.2 per 1000 person years
If early ART reduces risk by 50% => risk reduction 2.6 / 1000 person years
1 death averted per 385 person years of ART
- Will initiation of ART in people with CD4 count > 350 / 500 be funded ?
- Assessment of cost-effectiveness requires a model that takes account of reductions in incidence
Policy of initiation of treatment at CD4 counts > 350 may require cost justification
Study group on Death Rates at High CD4 count in ART naïve people. Lancet 2010
~ 90% of gay men have been tested for HIV
High rates of HIV testing but rising incidence ingay men in Australia
Wand et al, 2010, Prestage et al, 2008
Models of the impact of ART on transmission
ART can function as an effective prevention tool, even with high levels of drug resistance and risky sex
Velasco-Hernandez JX, Gershengorn HB, Blower SM. Lancet Inf Dis 2002
The use of treatment as prevention has the potential to reduce HIV epidemics only if consistent condom use is maintained.
Wilson et al, Lancet 2008
ART is predicted to have individual and public health benefits ...but the benefit can be lost by residual infectivity or …… sexual disinhibition...
Abbas UL, Anderson RM, Mellors JW. JAIDS 2006
ART cannot be seen as a direct transmission prevention measure, regardless of the degree of coverage
Baggaley RF, Garnett GP, Ferguson NM. PLoS Med 2006
Expansion of HAART (amongst those with CD4 < 200 / < 350) led to substantial reductions in the growth of the HIV epidemic and related costs Lima et al JID 2008
Predicted effects on HIV incidence depend onassumptions on:
- Testing coverage and frequency
- Effect on individual health of early ART
- Feasibility of identifying people in primary infection
- Durability of adherence / viral load suppression on ART
- Development and transmission of drug resistant virus
- Change in unprotected sex due to HIV diagnosis
- Change in unprotected sex due to viral suppression
- Extent of reduction in infectivity with ART
Fixed variables Variables updatedat infection over time
Years from infection
0 0.25 0.5 0.75 1.00 1.25
Calendar dateAge at infectionGenderPrimary resistance
Calendar dateAgeViral loadCD4 countRisk of AIDS / death
Use of specific ARVsResistance mutations
HIV synthesis modelCreates a ‘dataset’ of the course of infection and therapy for individual simulated patients.
HIV progression in absence of ART
PCP prophylaxis
Gender
Age
Viral load
CD4 count AIDS
Death from HIV
Death from other cause
Phillips et al, HIV Medicine 2007; Lancet 2008
Assumed 1.5-fold increased
Effect of ART
CD4 count
Phillips et al, HIV Medicine 2007, Lancet 2008
Death from HIV*
Acquisition of new resistance
mutations
Time on current regimen
Viral load
CD4 counts
AIDS*
*influenced by age and PCP prophylaxis also
Current adherence
# Active drugsin regimen
Switch tonext line of ART
Failure of current line
of ART
Effect of stopping ART
CD4 count
Phillips et al, HIV Medicine 2007, Lancet 2008
Death From HIV*
Viral load
CD4 counts
AIDS*
Probability of resuming ART
Time off ART
Loss from majority virus of
acquired resistance mutations
*influenced by age and PCP prophylaxis alsoOther processes include: - Loss to follow-up - Substitution of drugs due to toxicity
Fit to observed data
Phillips et al, HIV Medicine 2007
Observed Modelled
Natural history
AIDS by 10 years 46% 48%Median CD4 count at diagnosis of AIDS ~ 40 35 % dead by 1 year from initial AIDS 40% 45%
Effect of ART
Virologic failure by 7 years 27% 29%>1 resistance mutation by 7 yrs 19% 25%
Rate of viral rebound in those with < 50 cps/mL 3-6% per yr 6% per yr>1 resistance mutation to 3 classes by 6 yrs 4% 6%Mean CD4 count increase at 3 years 273 270
Additional variables updated over time
Years from 1985
1985 1985.25 1985.5 1985.75 1986.00 1986.25
e.g.Calendar dateInfection with HIVSexual risk behaviour:- Long term partnership status- Number of new partners
HIV transmission synthesis model: Heterosexual epidemic in southern Africa Creates a ‘dataset’ of the lifetime experiences of ~50,000 people in apopulation, aged over 15.
Number of new partners
Gender
Risk of HIV infection in uninfected subject
Probability ofHIV infection
Long term partner HIV+
Number of newpartners who are
HIV+
Number of new partnerships formed
by HIV+ people Current viralload of infectedpartner
Subject
ConcurrentHIV+ population
Incidence and prevalenceof HIV in people with
long term partnerships
Longterm partnership
status
Age
Risk of infection also depends on current STI
Comments
- In southern African heterosexual epidemic setting:
Assuming that unprotected sex with long term partners will reduce upon HIV diagnosis, a policy of frequent testing is likely to be beneficial for incidence, regardless of whether ART initiation threshold is CD4 200, CD4 350 or higher.
- Plans to adapt this model for MSM in UK
Conclusion
Models so far have demonstrated that intensive HIV testing with early ART initiation can, in principle, lead to substantial reductions in incidence if certain conditions hold.
Models required now are ones that will give as realistic and detailed assessment as possible of the predicted impact of frequent testing and early ART on HIV incidence, and thus enable estimation of cost-effectiveness of the approach.