US Government Spent Far More on Costly HIV PrEP Development Than Previously Thought

The US government spent far more money developing tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) for HIV pre-exposure prophylaxis (PrEP) than previously estimated, according to a study published in Health Affairs.

Based on 2022 inflation-adjusted dollars, the US government spent $314 million potentially related to TDF-FTC for PrEP development, including $143 million directly linked to development and clinical testing.

The previous estimate was over $50 million.

TDF and FTC have played a significant role in HIV treatment and containment over the past 2 decades. Initially approved by the FDA in 2001 and 2003, respectively, TDF and FTC were used to treat patients with HIV, and in 2004, the combination product TDF-FTC received FDA approval and was sold under the brand name Truvada by Gilead Sciences. Later in 2012, the FDA approved the combination therapy as the first daily regimen for HIV PrEP.

The US government had reportedly provided over $50 million in funding for the development of TDF-FTC for PrEP. In November 2019 and in response to concerns about the drug's high price, the government sued Gilead Sciences, alleging infringement of government patents for TDF-FTC as PrEP. In April 2020, Gilead countersued for breach of contract, and HHS and Gilead are still engaged in ongoing litigation regarding the ownership of key patents on the drug and its use in HIV prevention.

Taking another look at these estimates, researchers used FDA documents, peer-reviewed literature, patent records, court filings, and other publicly available materials to identify 46 key terms associated with the development of TDF-FTC for PrEP, which were linked to over 350,000 National Institutes of Health awards granted between 1998 and 2012.

Among these awards, only 73 had a cumulative relevancy score of 2 or 3, indicating their connection to TDF-FTC for PrEP research. These government awards were connected to 11 researchers as being directly linked to the development and clinical testing of TDF-FTC for HIV PrEP.

Through the National Institute of Allergy and Infectious Diseases, National Institute of Mental Health, and National Institute of Nursing Research, the US government spent an estimated $143 million in 2022 inflation-adjusted dollars, or a nominal dollar value around $111 million.

This new report also highlighted 5 specific principal investigators who received financial awards:

• Robert Grant, MD, MPH, professor of medicine at University of California San Francisco
• Gita Ramjee, PhD, South African Medical Research Council
• Kenneth Mayer, MD, medical research director and co-chair of the Fenway Community Health Center
• Peter Anderson, PharmD, professor of pharmaceutical sciences at the University of Colorado Anschutz Medical Campus
• Jared Baeten, MD, PhD, professor of global health, medicine, and epidemiology at the University of Washington

It may also be worth noting that Baeten later became the vice president of clinical development and HIV franchise head at Gilead Sciences, and has been serving in the position since October 2020.

Additionally, there were 3 main trials that received federal funding, in nominal and 2022 adjusted dollars, respectively:

• iPrEx (60,455,848 and 78,940,392)
• VOICE (48,290,919 and 61,402,951)
• Partners PrEP Study (2,347,450 and 2,895,896)

"Our estimate for highly related award values is larger than the often-cited $50 million estimate of government contribution to TDF-FTC for PrEP development, based on the iPrEx study,” the authors noted. “This is because we considered every TDF-FTC for PrEP clinical trial listed in the 2012 FDA summary review document, instead of focusing on just one of those trials."

The researchers also called this a conservative estimate, as they did not include potentially related awards, which would total $314 million. Additionally, their search methods were designed to minimize the inclusion of awards unrelated to TDF-FTC for PrEP development by focusing on specific authors and institutions, and the criteria used in their award search terms were intentionally conservative, which may have led to an underestimation of the full government contribution.

According to the researchers, these new estimates raise concerns about why US taxpayers have been paying excessively high prices for a life-saving medication that their money helped fund. Despite US government support, TDF-FTC had a list price of $1,600-$2,000 per month by 2019, while it was available for less than $6 in Australia. Additionally, the medication was available in generic form in many other high-income countries by 2019, despite the CDC holding patents related to it.

“What are fair returns on transformative medicines that are based so heavily on public-sector origins or funding, especially when high prices determined by the manufacturer make a life-saving medication unaffordable to many patients?” The authors asked. “Several approaches could have more fairly compensated the federal government for its contribution to TDF-FTC for PrEP development and justified lowering the regimen’s US price during the many years when that price was a major barrier to access.”

Reference

Tessema FA, Barenie RE, Avorn J, Kesselheim AS. Federal funding for discovery and development of costly HIV drugs was far more than previously estimated. Health Aff (Millwood). 2023;42(5):642-649. doi:10.1377/hlthaff.2022.01134