Not long ago, HIV was completely untreatable, but advances in both anti-viral treatments and HIV preventions are expanding the medical toolbox against this globally devastating virus. Specifically, pre-exposure prophylaxis (PrEP) successfully prevents new HIV infections, but it is costly and requires strict daily adherence to a drug. So, while an effective HIV vaccine remains desirable, one has yet to be developed. A future HIV vaccine could greatly complement PrEP and condom use, but will also pose competition for these prevention tools, which could affect the economic and perceived value of an HIV vaccine, as well as the policies surrounding vaccine rollout. Furthermore, a future HIV vaccine may not provide 100% protection from infection, making both vaccine and PrEP imperfect tools and further increasing the need to understand the tradeoffs of using one or both strategies in combination. To better understand the economic implications of potential interplay between these strategies, Blythe Adamson, formerly of the global HIV Vaccine Trials Network based at Fred Hutch, along with Dobromir Dimitrov and colleagues from the Vaccine and Infectious Disease Division and The Comparative Health Outcomes, Policy, and Economics (CHOICE) Institute at the University of Washington, developed a model to perform economic analysis of the cost-effectiveness of HIV vaccines. They published this work in the Journal of the International AIDS Society.
Currently, a major focus of HIV researchers around the world is on developing an HIV vaccine, and the Seattle area is a national leader in HIV research as well as implementation of novel HIV treatment and prevention strategies. In addition, Seattle has high rates of PrEP use among high risk populations such as men who sleep with men (MSM), making the Seattle area population data a good candidate for the authors’ health economic modeling analysis. To calibrate their model, the authors used empirical data from between 2004 and 2014 to simulate the HIV epidemic among MSM and extrapolate transmission rates and prevalence between the years of 2025 and 2045, incorporating published data on condom use tendencies, number of partners, and lifetime years of sexual activity. The model then considered the use of PrEP, beginning in 2015, as well as the use of a preventative vaccine, in 2025, and compared the transmission rates with one or both prevention measures added.
To account for the imperfections in both effectiveness and adherence to PrEP and effectiveness of a hypothetical vaccine, the model operated on several assumptions. The model used published data to estimate PrEP usage among Seattle MSM in 2025 to be is 25% (50% among high-risk MSM), and that due to incomplete adherence, effectiveness of PrEP is only 80%. Likewise, the model assumed 50% protection with the vaccine, with protective efficacy waning after five years. To predict the economic consequences of a vaccine, the model inferred costs based on the current expense of PrEP and treatment of HIV infection. However, the cost of a vaccine roll-out is unknown, so the authors chose to assume the vaccine costs about 30% more than the human papillomavirus vaccine, which is currently in use.
Although the authors hypothesized that the combined protective effects of condom use, PrEP, and vaccine usage would be multiplicative, they acknowledged that these interactions could potentially negate a vaccine’s clinical and economic value. To attempt to account for this interplay, the model assumed certain truths: PrEP is targeted to high-risk MSM while the vaccine would be suggested for all MSM, existing PrEP users are more likely to obtain an HIV vaccine, and vaccine recipients may continue PrEP after HIV vaccination.
With these considerations, the authors used the model to “understand the possible value of a modestly effective HIV vaccine if it were launched in Seattle in 2025,” as Adamson explained. For outcome metrics, the model calculated the number and percentage of new HIV infections that were prevented, reduction in HIV prevalence, and quality-adjusted life years (QALYs), which are an economic measure of disease burden. Based on these criteria, the model found that despite the costs of its introduction, an HIV vaccine would be cost-effective, as many life-long healthcare expenses in HIV treatment and PrEP medications could be avoided, off-setting the upfront financial burden of the vaccinating the population. Specifically, the model estimated that the introduction of a vaccine in 2025 would lead to an incremental cost-effectiveness ratio—a statistic used to weight the trade-offs of benefits and costs of a health care intervention compared to existing treatments—of 42,473 dollars per QALY gained compared to PrEP treatment alone. Interpreting this result using a common willingness-to-pay threshold of 150,000 dollars per QALY for a valuable medical innovation means an HIV vaccine would be cost-effective.
Adamson explained these results, acknowledging both the advantages and disadvantages of introducing a vaccine: “There are tradeoffs in the competition between two imperfect biomedical HIV prevention products. One aspect is the opportunity to vaccinate a larger fraction of the population than with PrEP alone. On the other hand, there is a downside from substitution of a highly effective and costly product, such as PrEP, with a less effective HIV prevention method.” Importantly, the authors warn that this cost benefit is dependent on the prevalence of PrEP usage and its cost at the time of vaccine introduction. Furthermore, people given an HIV vaccine believe themselves to be less at risk for HIV and therefore may be less likely to maintain consistent condom usage, would could lead to adverse outcomes and increased costs if they then become infected with other sexually transmitted infections or HIV itself, due to incomplete protection from the vaccine.
Dimitrov further explained the implications of their results. “The number of available options for effective HIV prevention is expected to grow in the near future with long-acting injectable PrEP and multi-dose HIV vaccines in the last stages of testing. Of public-health importance is the net increase of the overall population proportion using HIV prevention following the approval of new products instead of replacement of existing prevention methods,” While an effective HIV vaccine does not yet exist, this research prospectively addresses considerations that will likely arise upon its approval by FDA. Adamson said that the “results from this math modeling study are beginning to inform early planning considerations for the implementation of HIV vaccines in the future.” However, much more work like this is needed to fully understand the implications of concurrent HIV tools. Adamson elaborated on this point: “Health department guidelines and policies will need to be carefully designed to guide interactions between potentially competing biomedical HIV prevention strategies to optimize for the best health outcomes.”
This work was supported by the Agency for Healthcare Research and Quality, the University of Washington Center for AIDS Research, the National Institutes of Health, and the American Foundation for Pharmaceutical Education.
Adamson B, Garrison L, Barnabas RV, Carlson JJ, Kublin K, Dimitrov D. 2019. Competing biomedical HIV prevention strategies: potential cost-effectiveness of HIV vaccines and PrEP in Seattle, WA. Journal of the International AIDS Society. 2019 Aug;22(8):e25373. doi: 10.1002/jia2.25373.