Are Clade Specific HIV Vaccines a Necessity? An Analysis Based on Mathematical Models

• Rapid deployment of non-clade matched HIV vaccines would be an effective public-health strategy in high risk populations.
• Pursuit of further incremental increase in vaccine efficacy is justified and will result in better long term effectiveness.
• Reduced condom use by vaccinated individuals may diminish the advantage of the replacement vaccination strategy.
• Reliable surrogate markers of vaccine efficacy are needed to speed up the development of effective HIV vaccines.The HIV vaccine field has followed the concept of clade specific (clade matched) vaccines for over 30 years. We investigate the implementation of non-clade matched and clade specific vaccines by simulating the HIV epidemics in San Francisco and South Africa: two regions of the world where the epidemics are well characterized. Our analysis suggests that rapid deployment of a non-clade matched vaccine would be an effective public health strategy. The most effective 10-year vaccination strategy is to employ non-clade matched vaccines in highest risk populations followed by the rapid development of a more effective clade matched prototype.

As HIV-1 envelope immune responses are critical to vaccine related protection, most candidate HIV vaccines entering efficacy trials are based upon a clade specific design. This need for clade specific vaccine prototypes markedly reduces the implementation of potentially effective HIV vaccines. We utilized a mathematical model to determine the effectiveness of immediate roll-out of a non-clade matched vaccine with reduced efficacy compared to constructing clade specific vaccines, which would take considerable time to manufacture and test in safety and efficacy trials. We simulated the HIV epidemic in San Francisco (SF) and South Africa (SA) and projected effectiveness of three vaccination strategies: i) immediate intervention with a 20–40% vaccine efficacy (VE) non-matched vaccine, ii) delayed intervention by developing a 50% VE clade-specific vaccine, and iii) immediate intervention with a non-matched vaccine replaced by a clade-specific vaccine when developed. Immediate vaccination with a non-clade matched vaccine, even with reduced efficacy, would prevent thousands of new infections in SF and millions in SA over 30 years. Vaccination with 50% VE delayed for five years needs six and 12 years in SA to break-even with immediate 20 and 30% VE vaccination, respectively, while not able to surpass the impact of immediate 40% VE vaccination over 30 years. Replacing a 30% VE with a 50% VE vaccine after 5 years reduces the HIV acquisition by 5% compared to delayed vaccination. The immediate use of an HIV vaccine with reduced VE in high risk communities appears desirable over a short time line but higher VE should be the pursued to achieve strong long-term impact. Our analysis illustrates the importance of developing surrogate markers (correlates of protection) to allow bridging types of immunogenicity studies to support more rapid assessment of clade specific vaccines.