Pre-Exposure Prophylaxis (PrEP): Is It Cost-Effective?

In July 2012, the US Food and Drug Administration approved tenofovir disoproxil fumarate plus emtricitabine (TDF/FTC), as pre-exposure prophylaxis (PrEP) for HIV prevention. It based its approval on two large, randomized double-blind, placebo-controlled clinical trials that showed the treatment was safe and effective, significantly reducing the risk of infection in those who closely adhered to the drug regimen.^1,2

But in an age of increasingly limited resources, a major question remained: Is the treatment cost effective? Or, as James D. Shelton, MD, put it in a 2011 article in Science:  “Are (antiretroviral therapies) ARVs a magic bullet to stop the global epidemic in its tracks?”

Probably not, he wrote. Among the numerous reasons he listed (including concerns about adherence, mixed results in clinical trials, and continued risk among people who erroneously believe they’re protected) was “cost and human resources.” As he noted, less than half of people worldwide who are eligible for ARV are receiving treatment, despite the $5.7 billion spent on ARV in 2011.

“In a world currently beset with economic stress and with increasing emphasis on other compelling global health priorities, the prospect of increasing provision of ARVs severalfold seems unrealistic,” he wrote. “Furthermore, the cost would be cumulative, as survival improves and progressively more people take ARVs for treatment and prevention.”

A recent publication in the journal PLoS Medicine takes a closer look at the same issue, attempting to answer the question: Is PrEP cost effective? “[D]ecision makers need information translating the trial results into potential population level impact and cost-effectiveness,” the authors wrote, “to ensure that any additional investment will have the maximum possible effect on the epidemic.”

Researchers from the Netherlands and Great Britain conducted a systematic review of the published literature that modeled the impact and cost of PrEP scale-up in diverse settings, from the perspective of healthcare providers. Of 961 titles and abstracts retrieved, they evaluated 36 full-text articles and included 13 in the review.

The results:

•    Southern Africa: PrEP appears cost effective
•    United States: Mixed results when used in a population of men who have sex with men (MSM), although it could have a significant effect on the epidemic itself.
•    Peru: Cost-effective in an MSM population when used in addition to current prevention programs.
•    Ukraine: Not cost-effective when used as the only prevention program among people who inject drugs, and less effective when compared to either methadone maintenance therapy or methadone maintenance therapy and ART.

Here lead author Gabriela B. Gomez, PhD, of the Department of Global Health at the University of Amsterdam, offers insights about the study’s findings and its implications for public policy here and throughout the globe.

How did you conduct your study?
We reviewed the modeling studies available to date and provided a cross-setting comparison of cost-effectiveness estimates for PrEP scale up. We paid a lot of attention to the comparison of assumptions made across the models. This is because our aim was to highlight to policy makers that the results of a cost-effective analysis depends very much on the assumptions made by the modelers and some assumptions might have a bigger impact on the results than others.
 
Briefly describe the outcomes and their implications.
In particular, our review aims to help policy makers in assessing published cost-effectiveness analyses of PrEP programs. The main aspects that will determine the potential cost effectiveness estimates of a program are costs, epidemic context (generalized or concentrated epidemic), individual adherence level, PrEP program coverage, and the prioritization strategy chosen. For instance, cost will be an important consideration if PrEP is to be paid by a national health system.

What are some of the policy discussions/controversies around the use of PrEP?
There are quite a few policy controversies surrounding PrEP.  I think PrEP has a place in combination prevention, but how it is going to be implemented will depend very much on the levels of access to antiretroviral therapy (ART) people already infected with HIV have in each setting. Other issues I think will be of importance are adherence and the possibility of resistance emerging. The issue on resistance emergence is of particular relevance for policy makers as second-line treatment regimens will be more expensive.

Are these issues similar across countries or it is unique to the specific country?
I think these issues are setting-specific – both accessibility to ART and costs of second-line regimens. Additionally, issues on how to identify and access groups to prioritize and therefore ensure the biggest impact of PrEP are dependent on the epidemic context.
 
How does this paper contribute to the policy discussion and inform decision making around the use of public funding for PrEP?
We hope this paper will help the policy discussion by providing a comparison of modeling results that highlights the importance of critically assessing these results. It is hoped that it will help frame the discussions – providing a guide of five key aspects to be considered when planning any PrEP program scale up.
 
(Dr. Gomez also noted that the review has some limitations, such as the fact that the studies included were restricted in their geographical context, making it difficult to generalize the conclusions. Although she and her team compared cost effectiveness estimates using an internationally agreed threshold, each country has its own criteria for cost effectiveness and decision-making.)

References:

REFERENCES

1. Baeten JM, Donnell D, Ndase P,

et al.

Antiretroviral prophylaxis for HIV prevention in heterosexual men and women.

N Engl J Med

2012;367(5):399-410.
2. Thigpen MC, Kebaabetswe PM, Paxton LA,

et al.

Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana.

N Engl J Med

2012;367(5):423-434.