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Mathematical Models to investigate HIV trends in Australia

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

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Mathematical Models to investigate HIV trends in Australia

  1. 1. 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
  2. 2. The Australian HIV Epidemic <ul><li>HIV notifications have been on the rise, particularly in MSM in Victoria and Queensland </li></ul>
  3. 3. Objective <ul><li>Attempt to explain </li></ul><ul><ul><li>causes of the rise in HIV notifications </li></ul></ul><ul><ul><li>reasons for differences between States </li></ul></ul><ul><ul><li>focus on men who have sex with men </li></ul></ul><ul><li>Approach: use a mechanistic mathematical model to represent transmission dynamics </li></ul><ul><ul><li>combine biological, behavioural, epidemiological and clinical data </li></ul></ul>
  4. 4. Data sources <ul><li>Testing rates (Gay Periodic Surveys) </li></ul><ul><li>Condom usage in penile-anal intercourse (Gay Periodic Surveys) </li></ul>
  5. 5. Data sources <ul><li>Number of sexual partners (National Centre in HIV Social Research Reports) </li></ul><ul><ul><li>Behaviour change </li></ul></ul><ul><ul><ul><li>Post diagnosis </li></ul></ul></ul><ul><ul><ul><li>AIDS stage disease </li></ul></ul></ul><ul><li>Disclosure of serostatus in casual partners (Gay Periodic Surveys) </li></ul><ul><ul><li>80-90% in regular partners </li></ul></ul>
  6. 6. <ul><li>Treatment if detected in primary infection </li></ul>Data sources <ul><li>Treated cases that achieve viral suppression (AHOD; AIDS 2005, 19:179-84 ) </li></ul>
  7. 7. Structure of mathematical model
  8. 8. Other data and assumptions <ul><li>Disease progression between each stage </li></ul><ul><li>Mortality rates </li></ul><ul><li>Efficacy of condoms and condom usage with serostatus </li></ul><ul><li>Average viral load in primary, chronic, AIDS stages, successfully treated; treatment failure </li></ul><ul><li>Proportion of MSM who have other STIs (5-15%) </li></ul><ul><ul><li>Increases transmission probability by 2-5 fold </li></ul></ul>
  9. 9. Model output <ul><li>Without an increase in other STIs the other changes in behavioural and clinical properties cannot directly account for the increase in National HIV notifications </li></ul>
  10. 10. Other STIs
  11. 11. Other STIs required <ul><li>Change in other STIs required to describe data </li></ul><ul><ul><li>~5-fold nationally </li></ul></ul><ul><ul><li>~2-fold NSW </li></ul></ul><ul><ul><li>~11-fold VIC </li></ul></ul><ul><ul><li>~9-fold QLD </li></ul></ul>
  12. 12. Infectious syphilis notifications
  13. 13. <ul><li>Unprotected anal intercourse by itself cannot directly account for all of the increased transmission </li></ul><ul><li>Other STIs as cofactors have played a large role </li></ul><ul><li>Decreased condom usage may be indirectly responsible for the majority of transmission </li></ul><ul><li>Promoting condom usage, increasing testing rates, treatment in primary infection, and targeting STIs could be effective interventions </li></ul>Conclusions from modelling study
  14. 14. Response to the Swiss Consensus Statement: Does undetectable HIV viral load mean non-infectiousness?
  15. 15. <ul><li>HIV-positive people on effective antiretroviral therapy are sexually not infectious </li></ul><ul><ul><li>Completely suppressed viraemia, <40 copies/ml </li></ul></ul><ul><ul><li>Without other STIs </li></ul></ul><ul><ul><li>Must adhere to therapy </li></ul></ul><ul><ul><li>Effects to be evaluated regularly by physician </li></ul></ul>The Swiss Statement
  16. 16. <ul><li>Potentially unwarranted fear of transmission can be displaced, when the risk is actually small </li></ul><ul><ul><li>E.g. heterosexual couples attempting conception </li></ul></ul><ul><ul><li>Another risk reduction strategy for MSM? </li></ul></ul>Benefits
  17. 17. <ul><li>Potentially large reductions in condom use </li></ul><ul><ul><li>Leading to increased risk of transmission </li></ul></ul><ul><ul><li>Further magnified by non-adherence, viral ‘blips’, virological failure, other STIs, missing regular appointment with physician </li></ul></ul>Disadvantages
  18. 18. <ul><li>Various prospective and retrospective cohort studies provide evidence to support the statement </li></ul><ul><ul><li>Serodiscordant heterosexual couples </li></ul></ul><ul><ul><li>HIV-infected pregnant women </li></ul></ul><ul><li>There is no doubt that effective treatment lowers the risk of HIV transmission </li></ul>Support for the Swiss Statement
  19. 19. <ul><li>Study by Quinn et al. (2000) NEJM 342 (13) pp.921. </li></ul>
  20. 20. <ul><li>Study by Quinn et al. (2000) NEJM 342 (13) pp.921. </li></ul><ul><ul><li>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 </li></ul></ul><ul><ul><li>Mathematically, this translates to </li></ul></ul><ul><ul><ul><li>chance of HIV transmission per act in chronic infection </li></ul></ul></ul><ul><ul><ul><ul><li>~0.0005 for female-to-male </li></ul></ul></ul></ul><ul><ul><ul><ul><li>~0.001 for male-to-female </li></ul></ul></ul></ul><ul><ul><ul><ul><li>~0.01 for male-to-male </li></ul></ul></ul></ul>
  21. 22. <ul><li>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 </li></ul><ul><li>Consider an ‘effectively treated’ HIV-infected person </li></ul><ul><ul><li>A viral load of 10 copies/ml </li></ul></ul><ul><ul><li>In discordant sexual relationship (~100 acts per year) </li></ul></ul><ul><ul><li>Probability of transmission per year is approx. </li></ul></ul><ul><ul><ul><li>0.0021 for female-to-male </li></ul></ul></ul><ul><ul><ul><li>0.0043 for male-to-female </li></ul></ul></ul><ul><ul><ul><li>0.0425 for male-to-male </li></ul></ul></ul>
  22. 23. <ul><li>In a cohort of 100 serodiscordant couples followed for one year, the expected number of seroconversions would be </li></ul><ul><ul><li>0.22, 0.43, and 4.3 for F-to-M, M-to-F, and M-to-M </li></ul></ul><ul><li>The Quinn study observed no seroconversions out of 51 couples followed for less than 2 years </li></ul><ul><ul><li>This is not surprising from a probabilistic sense </li></ul></ul><ul><li>However, in a large population and over a long period of time significant numbers of seroconversions would be expected </li></ul>
  23. 27. <ul><li>In a population of 10,000 serodiscordant couples, in which the HIV-infected person is ‘effectively treated’, over 10 years (~1000 acts) </li></ul><ul><li>The expected number of seroconversions would be </li></ul><ul><ul><li>~215 for female-to-male transmission </li></ul></ul><ul><ul><li>~425 for male-to-female transmission </li></ul></ul><ul><ul><li>~3524 for male-to-male transmission </li></ul></ul><ul><li>HIV transmission in heterosexual partnerships is rare, but non-zero </li></ul><ul><li>HIV transmission in male homosexual partnerships could be surprisingly high </li></ul>
  24. 28. <ul><li>For Australian MSM, on antiretroviral therapy, viral suppression is achieved in ~85% of cases </li></ul><ul><li>If ~15% of treated cases had an inflated viral load of 1000 copies/ml the expected number of seroconversions would be </li></ul><ul><ul><li>~706 after 1 year </li></ul></ul><ul><ul><li>~4385 after 10 years </li></ul></ul><ul><li>Compare: ~104 and ~990 after 1 and 10 years under current conditions </li></ul><ul><li>Although the individual risk per act is relatively small, the rate of transmission over large numbers of acts is predicted to be substantial </li></ul>
  25. 29. <ul><li>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 </li></ul><ul><li>Population-level effects can be harmful, particularly among MSM </li></ul>

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