For the last two decades, the global distribution and ease of access for antiretroviral (ARV) drugs have transformed HIV from a death sentence to a manageable disease and prevented tens of millions of new infections when used as pre-exposure prophylaxis (PrEP). The remarkable new drug lenacapavir is a novel, first-in-class ARV that targets the HIV capsid, a protein shell that carries the viral genome. The capsid undergoes a process called uncoating, which allows the viral genome to be replicated and new virus particles to be produced. Lenacapavir blocks both the uncoating and assembly of new virus particles. Because of how tightly it binds the HIV capsid protein, disrupting its ability to function normally, it is much more difficult for the virus to evolve resistance.
Lenacapavir is not just the hot new ARV in town, it also exceeds every other drug on the market in terms of its durability. When lenacapavir is injected under the skin, it crystallizes and is then slowly released over months, providing sustained protection against HIV infection. It does not need to be taken orally every day, making it much more practical and less stigmatizing than existing PrEP regimens, particularly for women, who often face social or cultural pressures that discourage condom use or oral PrEP tablets.
The PURPOSE clinical trials demonstrated that lenacapavir prevents HIV infection in 99.9 percent of people receiving just two shots per year as PrEP. It shows great promise for treating multidrug-resistant infections, as well, giving hope to patients who are out of treatment options. Lenacapavir is poised to deal a crushing blow to the HIV pandemic by both treating previously untreatable infections and preventing new ones—but only as long as it’s available, something that’s now in jeopardy.
The use of ARVs has been deeply dependent on the U.S. Agency for International Development (USAID) and the President’s Emergency Plan for AIDS Relief (PEPFAR). Investments by USAID and PEPFAR in critical infrastructure, clinical expertise, and health care expanded access to ARVs around the world. Their budgets amounted to a rounding error relative to other U.S. spending yet returned massive value: 26 million lives saved by supporting ARV treatment, which is approximately 70 percent of the people taking HIV treatment globally.
In countries supported by PEPFAR, new HIV infections decreased by more than 50 percent. AIDS-related deaths fell even more. Nearly 8 million babies were born HIV-negative thanks to these programs, which also increased life expectancy by nearly 20 years in some places. They were also responsible for more than 90 percent of PrEP initiations, with more than 2.5 million people protected against HIV infection as a result. When lenacapavir came on the scene, it was immediately apparent that it could revolutionize PrEP by leveraging what USAID and PEPFAR had built.
The U.S. Food and Drug Administration approved lenacapavir for PrEP in June. Under any other circumstances, this would be cause for celebration—but not in the current U.S. political landscape. PEPFAR has sustained catastrophically ruinous cuts, while USAID has been dismantled to the core. These cuts have forced clinics to close, put health care workers out of work, and, most critically, caused people to go off their ARV medication.
Countries that received PEPFAR support experienced accelerated economic growth as a result of reduced HIV mortality in their workforces. As HIV-related deaths return to these countries along with dwindling U.S. support, their economies will suffer, further eroding national health care resources and availability.
This is very bad news for lenacapavir’s potential to deliver the coup de grace to the HIV pandemic. Revolutionary new drugs only work if the people who need them can get them. Without the infrastructure supported by PEPFAR and USAID, millions of people at risk for contracting HIV will lack access to lifesaving medication.
When combined with lack of access to ARV medication, more drug-resistant HIV strains are likely to emerge, since this is a known consequence of patchy adherence to daily treatment regimens. This could contribute to an HIV landscape that is even more dire than prior to PEPFAR: HIV deaths will increase and return to pre-PEPFAR levels, except now they will be caused by viruses that are harder to treat and easier to spread.
Another issue concerns costs. Lenacapavir’s manufacturer, Gilead, introduced the drug with a tiered pricing scheme in which it costs $28,000 per year for PrEP and $42,000 per year for multidrug-resistant HIV treatment. Studies estimating that generic lenacapavir could be manufactured for as little as $25 per year prompted the United Nations AIDS agency to urge Gilead to lower its prices. This is eerily reminiscent of the time before PEPFAR, when people in wealthy countries had access to ARV treatments while millions of people in the global south died of AIDS.
Although Gilead has developed a “no-profit” model to grant nonexclusive, royalty-free licenses to manufacture lenacapavir as a generic drug in low- and lower-middle-income countries, the cost of producing it is still prohibitive. The “no-profit” pricing excludes many middle-income countries in Latin America, where HIV infections are on the rise. Dismantling PEPFAR and USAID will likely constrain access to lenacapavir and other ARV medications in these countries, resulting in an entirely new landscape of countries that are unable to halt rising HIV infection rates. Without the accompanying investments in infrastructure, training, and health systems, millions more people will suffer from HIV for no other reason than shortsighted, nihilistic U.S. policymakers.
In the United States, National Institutes of Health (NIH) Director Jay Bhattacharya has ideas for integrating lenacapavir into public health policies for HIV prevention. Bhattacharya has floated a plan to devote $1 billion to implementing lenacapavir PrEP nationwide. However, this would strip funding from other basic HIV research programs, such as the NIH-funded research that led to lenacapavir’s discovery in the first place, as well as HIV vaccine research that U.S. Health and Human Services Secretary Robert F. Kennedy Jr. has dismissed as worthless. The additional job losses caused by the Trump administration defunding entire health-related research and implementation programs—both within and external to the government—will further decrease the NIH’s ability to support national access to lenacapavir PrEP.
As the Trump administration dismantles biomedical science and public health capacity in the United States and thus hinders efforts to fight HIV globally, it becomes increasingly difficult to understand how Bhattacharya’s plan to unlock lenacapavir would meaningfully reduce the burden of HIV domestically, much less end it globally.
PEPFAR was established by former U.S. President George W. Bush, a conservative Republican who viewed it as a moral imperative for the United States to contribute to global health. It is clear that the Trump administration does not consider itself responsible for prior commitments to the world or even to Americans.
It is both ironic and deeply tragic that the United States is deliberately abdicating its leadership in the fight against the HIV pandemic at the same time that a game-changing drug such as lenacapavir emerges on the market. It is not clear that any other country has the funds, freedom, infrastructure, or a national sense of moral obligation to fill the void.
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