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Nico Nagelkerke

Heterogeneity in host HIV susceptibility as a potential contributor to recent HIV prevalence declines in Africa. Nico Nagelkerke. HIV prevalence declines in many high prevalence areas in SS Africa.

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Nico Nagelkerke

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  1. Heterogeneity in host HIV susceptibility as a potential contributor to recent HIV prevalence declines in Africa Nico Nagelkerke

  2. HIV prevalence declines in many high prevalence areas in SS Africa

  3. In some of the hardest hit countries this started earliest, but happens everywhere prevalence/incidence was high Source: http://www.iavireport.org/Issues/Issue11-3/IR_MayJun07.pdf

  4. Two causes have been suggested • Behaviour change (more condoms, fewer partners) • Success of intervention programmes • ABC, Sex worker programmes, Voluntary Counselling and Testing • Perhaps in combination with seeing friends and relatives die from AIDS • Maturing epidemic, higher mortality • As hazard rate of dying increases with time after infection, mortality lags behind incidence by about a decade

  5. Change in prevalence sometimes presented as evidence of impact behaviour change HIV Decline Associated with Behavior Change in Eastern Zimbabwe. Science 3 February 2006 Simon Gregson,1,2* Geoffrey P. Garnett,1 Constance A. Nyamukapa,2 Timothy B. Hallett,1 James J. C. Lewis,1 Peter R. Mason,2 Stephen K. Chandiwana,2,3 Roy M. Anderson1 Few sub-Saharan African countries have witnessed declines in HIV prevalence, and only Uganda has compelling evidence for a decline founded on sexual behavior change. We report a decline in HIV prevalence in eastern Zimbabwe between 1998 and 2003 associated with sexual behavior change in four distinct socioeconomic strata. HIV prevalence fell most steeply at young ages—by 23 and 49%, respectively, among men aged 17 to 29 years and women aged 15 to 24 years—and in more educated groups. Sexually experienced men and women reported reductions in casual sex of 49 and 22%, respectively, whereas recent cohorts reported delayed sexual debut. Selective AIDS-induced mortality contributed to the decline in HIV prevalence.

  6. Yet there are other factors In a Kenyan cohort of sex workers (FSW) the risk of infection per unprotected contact fell dramatically-before declines in HIV in clients Kimani J, Kaul R, Nagelkerke NJ, Luo M, MacDonald KS, Ngugi E, Fowke KR, Ball BT, Kariri A, Ndinya-Achola J, Plummer FA. Reduced rates of HIV acquisition during unprotected sex by Kenyan female sex workers predating population declines in HIV prevalence. AIDS. 2008

  7. Why? • Simplest explanation: not everybody equally susceptible to HIV infection • Empirical evidence for host susceptibility, e.g. • CCR5 polymorphisms can protect against HIV • Resistant sex workers in Kenya, • with genetic correlates • Most infections occur early during a partnership - few later on

  8. Can heterogeneity in host susceptibility explain decline in FSW? • Used (too) simple compartmental model • With 4 levels of host susceptibility (to be fitted)

  9. FSW data: model fit

  10. Population data: model fit

  11. Comments • Fitted to FSW data only • Ignored both behavior change AND excess mortality • To see effect of host susceptibility alone • Overestimates % totally resistant (40%) • Due to discrete levels of susceptibility

  12. Implications • Complicates our ability to attribute changes in HIV prevalence to behaviour change • High number of transmission events are attributed to individuals with very early HIV infection, but may be due to heterogeneity in susceptibility NOT infectiousness • Concept of “risk per sexual contact” (used by many mathematical models) is misleading • Useful cross-sectionally, but not dynamically • Ergodic fallacy

  13. To appear in AIDS (2008?). • Thank you very much!! شكراً

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