Session 114Poster Presentations HIV Transmission Session Day and Time: Tuesday 1:30 - 3:30 pm Room: Hall B
899 Predicting the Ability of Non-sterilizing Vaccines to Control the HIV Epidemic M. P. Davenport*1, D. L. Chao2, R. M. Ribeiro3, A. S. Perelson3 1Univ of New South Wales, Sydney, Australia; 2Univ of New Mexico, Albuquerque; and 3Los Alamos Natl Lab, NM
Background: Studies of HIV vaccination in monkeys suggest that CTL vaccines are unable to prevent infection, but they may reduce viral loads and mortality in chronic infection. If such vaccines can be developed for humans, they will clearly be beneficial to infected individuals. However, it is unclear what impact they would have on the epidemic. A number of factors may limit the ability of a vaccine to reduce the size of the epidemic: short duration of vaccine effectiveness, increases in risk behavior of vaccinees, and development and transmission of escape mutant virus. We assessed the long-term impact of a vaccine that modifies the course of disease without preventing infection.
Methods: We developed an epidemiological model of heterosexual HIV transmission structured by age and duration of infection. The novelty of this approach is that it allows consideration of intra-host dynamics such as the rate of disease progression. Because of the uncertainty in the effects of the vaccine (reduction in viral load, slower disease progression, increased sexual risk behavior, and time for escape to occur) we used a simulation approach in which parameter values are randomly sampled from a range of possible values. We then performed a risk and sensitivity analysis on the results.
Results: A vaccine that reduces viral load following infection by 0.5 to 1.5 logs would reduce the number of HIV associated deaths by 27% to 92% by 25 yrs. The proportion of individuals vaccinated, the increase in risky sexual behavior, and the decrease in viral load following vaccination are all significantly correlated with long-term mortality (r = -0.81, 0.53, and 0.50, respectively). Surprisingly, disease progression rate and rate of viral escape had little effect on the long-term outcome of the epidemic.
Conclusions: Disease modifying vaccines that are unable to prevent infection could significantly reduce the number of HIV infections and deaths. Increases in sexual risk behavior are predicted to lead to an increase in HIV incidence over the first years after introduction of the vaccine, but in the long-term new infections and deaths are predicted to decrease. Thus, in clinical trials, the short-term effect of a vaccine on HIV incidence may not be predictive of its long-term ability to control infection. The reduction in viral load following infection is an important predictor of the ability of the vaccine to reduce transmission and should be carefully monitored.
