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Mathematical Models to investigate HIV trends in Australia
 

Mathematical Models to investigate HIV trends in Australia

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This presentation was given at the 2008 AFAO HIV Educators conference.

This presentation was given at the 2008 AFAO HIV Educators conference.

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    Mathematical Models to investigate HIV trends in Australia Mathematical Models to investigate HIV trends in Australia Presentation Transcript

    • Mathematical models to investigate recent HIV trends in Australia David Wilson , Alex Hoare, David Regan, John Kaldor, Matthew Law National Centre in HIV Epidemiology and Clinical Research, University of New South Wales David Wilson , Andrew Grulich, Matthew Law, David Cooper, John Kaldor Implications of the Swiss Consensus Statement [email_address] Reference group: Frank Bowden, Sharon Flanagan, John Imrie, Phillip Keen, Rosemary Lester, Kelly Shaw, Bill Whittaker
    • The Australian HIV Epidemic
      • HIV notifications have been on the rise, particularly in MSM in Victoria and Queensland
    • Objective
      • Attempt to explain
        • causes of the rise in HIV notifications
        • reasons for differences between States
        • focus on men who have sex with men
      • Approach: use a mechanistic mathematical model to represent transmission dynamics
        • combine biological, behavioural, epidemiological and clinical data
    • Data sources
      • Testing rates (Gay Periodic Surveys)
      • Condom usage in penile-anal intercourse (Gay Periodic Surveys)
    • Data sources
      • Number of sexual partners (National Centre in HIV Social Research Reports)
        • Behaviour change
          • Post diagnosis
          • AIDS stage disease
      • Disclosure of serostatus in casual partners (Gay Periodic Surveys)
        • 80-90% in regular partners
      • Treatment if detected in primary infection
      Data sources
      • Treated cases that achieve viral suppression (AHOD; AIDS 2005, 19:179-84 )
    • Structure of mathematical model
    • Other data and assumptions
      • Disease progression between each stage
      • Mortality rates
      • Efficacy of condoms and condom usage with serostatus
      • Average viral load in primary, chronic, AIDS stages, successfully treated; treatment failure
      • Proportion of MSM who have other STIs (5-15%)
        • Increases transmission probability by 2-5 fold
    • Model output
      • Without an increase in other STIs the other changes in behavioural and clinical properties cannot directly account for the increase in National HIV notifications
    • Other STIs
    • Other STIs required
      • Change in other STIs required to describe data
        • ~5-fold nationally
        • ~2-fold NSW
        • ~11-fold VIC
        • ~9-fold QLD
    • Infectious syphilis notifications
      • Unprotected anal intercourse by itself cannot directly account for all of the increased transmission
      • Other STIs as cofactors have played a large role
      • Decreased condom usage may be indirectly responsible for the majority of transmission
      • Promoting condom usage, increasing testing rates, treatment in primary infection, and targeting STIs could be effective interventions
      Conclusions from modelling study
    • Response to the Swiss Consensus Statement: Does undetectable HIV viral load mean non-infectiousness?
      • HIV-positive people on effective antiretroviral therapy are sexually not infectious
        • Completely suppressed viraemia, <40 copies/ml
        • Without other STIs
        • Must adhere to therapy
        • Effects to be evaluated regularly by physician
      The Swiss Statement
      • Potentially unwarranted fear of transmission can be displaced, when the risk is actually small
        • E.g. heterosexual couples attempting conception
        • Another risk reduction strategy for MSM?
      Benefits
      • Potentially large reductions in condom use
        • Leading to increased risk of transmission
        • Further magnified by non-adherence, viral ‘blips’, virological failure, other STIs, missing regular appointment with physician
      Disadvantages
      • Various prospective and retrospective cohort studies provide evidence to support the statement
        • Serodiscordant heterosexual couples
        • HIV-infected pregnant women
      • There is no doubt that effective treatment lowers the risk of HIV transmission
      Support for the Swiss Statement
      • Study by Quinn et al. (2000) NEJM 342 (13) pp.921.
      • Study by Quinn et al. (2000) NEJM 342 (13) pp.921.
        • Calculated a rate ratio of 2.45 (95% CI, 1.85-3.26) Increase in HIV transmission for every log 10 increase in viral load
        • Mathematically, this translates to
          • chance of HIV transmission per act in chronic infection
            • ~0.0005 for female-to-male
            • ~0.001 for male-to-female
            • ~0.01 for male-to-male
    •  
      • Assuming each sexual act between serodiscordant people is independent of other acts in terms of the chances of HIV transmission, we can estimate the probability of transmission over a partnership of numerous acts for given viral load
      • Consider an ‘effectively treated’ HIV-infected person
        • A viral load of 10 copies/ml
        • In discordant sexual relationship (~100 acts per year)
        • Probability of transmission per year is approx.
          • 0.0021 for female-to-male
          • 0.0043 for male-to-female
          • 0.0425 for male-to-male
      • In a cohort of 100 serodiscordant couples followed for one year, the expected number of seroconversions would be
        • 0.22, 0.43, and 4.3 for F-to-M, M-to-F, and M-to-M
      • The Quinn study observed no seroconversions out of 51 couples followed for less than 2 years
        • This is not surprising from a probabilistic sense
      • However, in a large population and over a long period of time significant numbers of seroconversions would be expected
    •  
    •  
    •  
      • In a population of 10,000 serodiscordant couples, in which the HIV-infected person is ‘effectively treated’, over 10 years (~1000 acts)
      • The expected number of seroconversions would be
        • ~215 for female-to-male transmission
        • ~425 for male-to-female transmission
        • ~3524 for male-to-male transmission
      • HIV transmission in heterosexual partnerships is rare, but non-zero
      • HIV transmission in male homosexual partnerships could be surprisingly high
      • For Australian MSM, on antiretroviral therapy, viral suppression is achieved in ~85% of cases
      • If ~15% of treated cases had an inflated viral load of 1000 copies/ml the expected number of seroconversions would be
        • ~706 after 1 year
        • ~4385 after 10 years
      • Compare: ~104 and ~990 after 1 and 10 years under current conditions
      • Although the individual risk per act is relatively small, the rate of transmission over large numbers of acts is predicted to be substantial
      • Although there is little risk of HIV transmission if ‘effective treatment’ alone is used for prevention, it does not make the Swiss consensus statement a sensible public health message
      • Population-level effects can be harmful, particularly among MSM