Pre-exposure prophylaxis (PrEP)—an HIV prevention intervention consisting of a daily drug cocktail, quarterly HIV/sexually transmitted disease screening, and laboratory monitoring—has repeatedly been shown to be safe, effective, and cost-effective. Although US guidelines have recommended PrEP for all high-risk individuals since 2014, fewer than 200,000 of the 1.2 million eligible Americans are enrolled in a PrEP program. The burden of inadequate coverage is borne disproportionately by the nation’s most vulnerable communities.
One word, more than any other, explains our national failure to expand PrEP coverage: cost. In a May 16, 2019, hearing entitled, “HIV Prevention Drug: Billions in Corporate Profits after Millions in Taxpayer Investments,” the Congressional House Oversight and Reform Committee heard testimony related to the cost of the approved HIV prevention drug combination, Truvada (tenofovir disoproxil fumarate/emtricitabine). For many PrEP-eligible individuals who either lack adequate health insurance coverage or who intentionally choose not to access it, the price of Truvada (approximately $20,000/year) is the most insurmountable obstacle.
Recent developments fuel the hope that relief is coming: first, the inclusion of PrEP in the Trump administration’s plan to end AIDS; second, the assignment of a Grade A recommendation to PrEP by the US Preventive Services Task Force (USPSTF); third, the announcement by Gilead that it will donate Truvada for up to 200,000 individuals; and finally, the earlier-than-anticipated arrival of generic alternatives to Truvada. While each of these developments should be greeted with favor, we believe that PrEP disparities will persist and that the retail price of PrEP drugs will remain the principal barrier to access for the foreseeable future.
Lesson #1: PrEP ≠ Magic Bullet
First things first: No single intervention will be sufficient to stop the HIV epidemic. The New York Times has referred to Truvada as “the drug that could end HIV.” More realistically, PrEP is a necessary but insufficient element of a comprehensive HIV eradication strategy that includes prevention and surveillance alongside HIV screening, detection, linkage to care, and sustained virologic suppression. Landmark trials consistently demonstrate PrEP’s exceptional efficacy (97 percent) in reducing HIV incidence among those with high drug adherence. However, several independent mathematical modeling studies find that even 90 percent–100 percent sustained PrEP coverage among men who have sex with men will avert no more than 50 percent of the new infections over the next 20 years; 40 percent–50 percent PrEP coverage might avert 29 percent–33 percent of new infections. A simple extrapolation of these findings (exhibit 1) shows that coverage would need to be near-complete—think herd immunity—before PrEP alone could exert meaningful impact on the long-term presence of HIV in the population.
Exhibit 1: Transmissions averted as a function of PrEP coverage
Sources: Jenness SM, Goodreau SM, Rosenberg E, Beylerian EN, Hoover KW, Smith DK, et al. Impact of the Centers for Disease Control’s HIV preexposure prophylaxis guidelines for men who have sex with men in the United States. J Infect Dis. 2016:214(12):1800-7; Juusola JL, Brandeau ML, Owens DK, Bendavid E. The cost-effectiveness of preexposure prophylaxis for HIV prevention in the United States in men who have sex with men. Ann Intern Med. 2012;156(8):541-50; Hamilton DT, Rosenberg ES, Jenness SM, Sullivan PS, Wang LY, Dunville RL, et al. Modeling the joint effects of adolescent and adult PrEP for sexual minority males in the United States. PLoS One. 2019;14(5):e0217315. Notes: Transmissions averted as a function of PrEP coverage: Results from three different HIV modeling studies portray the relationship between the proportion of individuals at high risk receiving PrEP (that is, the “coverage,” horizontal axis) and the percentage reduction in HIV transmissions (that is, “transmissions averted,” vertical axis). A power curve fit to these data (equation shown) suggests positive but diminishing marginal returns to increased investment in PrEP coverage. *Of note, Juusola JL, et al., models HIV incidence reduction over a longer time horizon than Jenness SM, et al., and Hamilton DT, et al. However, when graphed separately, slopes are not significantly different.
Lesson #2: More Affordable PrEP = More Effective HIV Prevention
The Law of Demand is a basic tenet of microeconomics: All other things being equal, lower prices elicit greater demand for a given good or service. Limited evidence permits us to apply the Law of Demand to PrEP and to appraise the damage that high Truvada prices are inflicting on the spread of HIV. In exhibit 2, we estimate the relationship between the retail price in US dollars of Truvada and the resultant PrEP coverage, using data from two resource-rich settings: the US ($20,000/year, 17 percent coverage) and Australia ($340/year, 61 percent coverage). Together, exhibits 1 and 2 permit us to estimate total downstream HIV transmissions averted at any given Truvada price (exhibit 3).
Exhibit 2: PrEP coverage as a function of PrEP price
Sources: Department of Health and Human Services. Washington (DC): HHS; 2019. Press release, Trump administration secures historic donation of billions of dollars in HIV prevention drugs; 2019 May 6; Centers for Disease Control and Prevention. Atlanta (GA): CDC; 2018. Press release, HIV prevention pill not reaching most Americans who could benefit—especially people of color;2018 Mar 6; AIDSinfo. What’s new in the guidelines? Rockville (MD): AIDSinfo; 2019 Jul 10; PrEPWatch. Australia: a snapshot of PrEP scale-up, registration and resources for Australia. New York (NY): PrEPWatch; 2019 Jul 26; Zablotska IB, Gray R, Whittaker B, Holt M, Wright E, Prestage G, et al. The estimated number of potential PrEP users among gay-identifying men who have sex with men in Australia. PLoS One. 2018;13(10):e0204138; PrEPaccessNOW. Australian Pharmaceutical Benefits Scheme. Melbourne: PAN; 2019. Notes: PrEP coverage as a function of PrEP price: Results from both US and Australian settings portray the relationship between the monthly price of PrEP (horizontal axis) and the proportion of individuals at high risk receiving PrEP (that is, the “coverage,” vertical axis). A linear association is assumed in fitting a PrEP demand curve (equation shown). Sensitivity analyses examine theoretical maximum coverage if PrEP costs were free: Under the Optimistic Scenario (dashed blue line), a maximum coverage of 75 percent could be achieved if PrEP drugs were available at no cost; Under the Pessimistic Scenario (dashed green line), a maximum coverage of 25 percent would result if PrEP drugs were available at no cost.
Exhibit 3: Transmissions averted as a function of PrEP price
Source: Authors’ analysis. Notes: Transmissions averted as a function of PrEP coverage: Results obtained from Panels A and B are combined to portray the impact of the monthly price of PrEP (horizontal axis) on the percentage reduction in HIV transmissions (vertical axis). The Optimistic and Pessimistic Scenarios show the proportion of transmissions that might be averted if maximum coverage with PrEP drugs at no cost were 75 percent and 25 percent, respectively.
Admittedly, this is a crude approximation. The price of Truvada to the end consumer is mediated by a tangled web of different payers, vouchers, copayments, and rebates, making it difficult to decipher who is generating what level of demand. Moreover, a 2017 study from the Centers for Disease Control and Prevention suggests that fewer than 1 percent of the eligible population may need financial assistance to obtain PrEP medications and care. However, this analysis employed data from the National Health and Nutrition Examination Survey, a national household survey that poorly represents the younger (adolescent) and often disproportionately homeless PrEP-eligible population.
These weaknesses notwithstanding, the lessons are clear: No extent of price cutting will be sufficient to eliminate HIV transmission; but a reduction in the current US retail price of Truvada compared to that which prevails in Australia could more than double the number of HIV transmissions averted each year.
Lesson #3: Gifts + Guidelines + Generics < Price Reduction
Recent developments create the impression that the financial barriers blocking access to PrEP may be crumbling. We worry that each will exert far less beneficial impact than anticipated.
Gifts
In May 2019, the Trump administration announced a commitment from Gilead to provide free access to Truvada for up to 200,000 individuals annually for an 11-year duration. This has been labeled a “historic donation of billions of dollars.” Health and Human Services secretary Alex Azar stated that “for individuals who might otherwise not be able to access or afford this important treatment…this agreement will help close that gap substantially.” The Gilead donation offers substantial relief to the lucky 200,000, but it exerts zero impact on the retail price of Truvada. And, contrary to Secretary Azar’s assertion, it leaves 80 percent of the approximately 1 million people who need PrEP no better off. Indeed, the greatest beneficiary may be Gilead itself: Since the value of a charitable gift may be based on its market value, a donation that exerts no downward pressure on the retail price could permit Gilead to pocket a tax deduction worth a billion dollars for a gift costing the company as little as $14 million per year.
Guidelines
In June 2019, the USPSTF issued a long overdue Grade A recommendation for PrEP. Since most US public and private insurers use the USPSTF grading scheme to guide their decisions about which preventive services to cover, this announcement might be expected to greatly expand access to PrEP drugs at no out-of-pocket cost. However, 21 of 48 US counties with the highest rates of new HIV diagnoses lie in states that have not yet expanded Medicaid. In these—the highest-need counties in the nation—the USPSTF recommendations will have no impact on public insurance coverage for PrEP. Moreover, many individuals at highest risk for HIV infection intentionally steer clear of insurance coverage for their PrEP needs. Lesbian, gay, bisexual, transgender, and questioning (LGBTQ) youth who are still on their parents’ insurance, for example, frequently avoid filing an insurance claim for fear that doing so would “out” them to their family. Finally, it is not clear whether the new USPSTF guidance will also trigger expanded indemnification for critical PrEP-associated services, including quarterly screening for HIV and sexually transmitted infections, laboratory monitoring, and behavioral counseling. People who struggle to afford insurance could be discouraged from initiating PrEP by the magnitude of these out-of-pocket ancillary costs.
Generics
While Gilead has announced that it will license Truvada to a single generic competitor (Teva) in September 2020, one year ahead of its scheduled patent expiration, significant price reductions typically result only after the entry of several generic competitors. We are unlikely to see several generic Truvada competitors for at least 2–5 years. Moreover, Gilead has requested Food and Drug Administration approval for Descovy (tenofovir alafenamide/emtricitabine)—a close cousin of Truvada that has been shown to be non-inferior and marginally safer when used for PrEP—in August 2019. As part of its much larger effort to promote Descovy as the agent of choice for PrEP, Gilead has signaled that it will transition people benefitting from its donation of Truvada to Descovy, once it is approved for use as PrEP. If this effort succeeds, generic Truvada will compete for an ever-decreasing share of the PrEP market, while hundreds of thousands of the neediest individuals receiving PrEP will have been funneled to a barely better drug that remains under Gilead’s monopolistic pricing control.
∑ Evidence = Conclusions
While substantially lower PrEP drug costs will not end the US epidemic, they will serve to avert many more transmissions than the current status quo. Donations, USPSTF endorsements, and generic equivalents may each result in modest near-term incremental benefits but they will certainly serve as no substitute for a good old-fashioned price cut. Class dismissed.
Authors’ Note
The authors would like to thank Nicole McCann for her technical assistance.