The utility of live attenuated vaccines for controlling HIV epidemics is being debated. Live attenuated HIV vaccines (LAHVs) could be extremely effective in protecting against infection with wild-type strains, but may not be completely safe as the attenuated strain could cause AIDS in some vaccinated individuals. We present a theoretical framework for evaluating the consequences of the tradeoff between vaccine efficacy (in terms of preventing new infections with wild-type strains) and safety (in terms of vaccine induced AIDS deaths). Elsewhere, we use our framework and uncertainty analyses to predict, for Zimbabwe and Thailand, the epidemiological impact of 1,000 different (specified by efficacy and safety characteristics) LAHVs. We predict that paradoxically: (i) in Zimbabwe (where transmission is high) LAHVs would significantly decrease the AIDS death rate, but (ii) in Thailand (where transmission is low) exactly the same vaccines (in terms of efficacy and safety characteristics) would increase the AIDS death rate. Our uncertainty analyses results imply that a threshold transmission rate exists that determines whether any given LAHV has a beneficial or a detrimental impact. We also determine the vaccine perversity point, which is defined in terms of the fraction of vaccinated individuals who progress to AIDS as a result of the vaccine strain. Detailed sensitivity analyses reveal that vaccination with any LAHV that causes more than 5% of vaccinated individuals to progress to AIDS in 25 years would, even 50 years later, lead to perversity (i.e., increase the annual AIDS death rate) in Thailand; these same vaccines would lead to decreases in the annual AIDS death rate in Zimbabwe.
For a link to the flow diagram of the equations used in the paper click here. This model and the results have been presented in the following article:
Here you can run the model yourself and see the potential impact of LAHVs in Zimbabwe and Thailand. You can vary vaccination coverage, vaccine efficacy and vaccine safety levels.
Instructions
First, please note that these applets are viewed best at resolutions of 800 x 600 or higher. If you are having a hard time running these applets because they don't fit on the screen, try clicking the 'Open without Frames' button at the bottom of this page. Also some browsers, such as the internet explorer have full screen modes, which enable more of a page to be displayed (for IE 5.0 the F11 key switches to the full screen mode).
In both applets we look at the effect of a live attenuated HIV vaccine (LAHV) on the annual death rate per 100,000 people. Note that while the vaccine (specified by the default parameters) has a positive impact in a country with a high HIV prevalence as in Zimbabwe (Applet 1.), it actually causes an increase to the annual AIDS death rate in a country with low prevalence like Thailand (Applet 2.).
To change a parameter in the model just select the parameter you want to change by using the drop box. Enter the new value for the parameter in the text box and click the 'Set' button. You can change the following parameters:
To run the simulation click on the 'Graph' button. Each time you hit the 'Graph' button the simulation advances time by another 50 years.
