Live Attenuated HIV Vaccines: Predicting the Tradeoff between Efficacy and Safety

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 98; no. 6; pp. 3618 - 3623
• Main Authors: Blower, S. M., Koelle, K., Kirschner, D. E., Mills, J.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 13-03-2001; National Acad Sciences; The National Academy of Sciences
• Subjects: Acquired Immunodeficiency Syndrome - mortality; Acquired Immunodeficiency Syndrome - prevention & control; Acquired Immunodeficiency Syndrome - virology; AIDS; AIDS Vaccines - immunology; Biological Sciences; Blowers; Consumer Product Safety; Disease progression; Disease transmission; Epidemics; HIV; HIV Infections - epidemiology; HIV Infections - mortality; HIV Infections - prevention & control; HIV Infections - virology; HIV-1 - immunology; Human immunodeficiency virus; Humans; Infections; Mass immunization; Models, Immunological; Mortality; Predictions; Predictive Value of Tests; Thailand; Thailand - epidemiology; Vaccination; Vaccines; Vaccines, Attenuated - immunology; Zimbabwe; Zimbabwe - epidemiology; Thailand; Zimbabwe
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.061029998

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). We use our framework 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 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. 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.