“The emerging data surrounding lenacapavir is so astonishing that the drug’s development has been heralded as the 2024 Breakthrough of the Year by the journal Science, which described it as representing ‘a pivotal step toward diminishing HIV/AIDS as a global health crisis.’”
David Cox, NPR’s Goats and Soda blog
“An approach grounded in human rights, combined with a biomedical, behavioural and structural response, is needed to curtail the HIV/AIDS pandemic once and for all.”
The Lancet
The World Health Organization (WHO) has a goal to end the HIV/AIDS pandemic by 2030. The goal of the Joint United Nations Programme on HIV/AIDS is to achieve zero new HIV infections, zero discrimination, and zero AIDS-related deaths by 2030. These goals are merited, but may be overly ambitious.
Over 42.3 million people globally have died of HIV/AIDS since 1981when the first cases of the disease were reported in the U.S. In 2023, an estimated 630,000 people lost their lives due to HIV-related causes. The 43 year battle against HIV/AIDS is marked with enormous tragedy but also with incredible achievements. Recently, scientists recognized the remarkable impact that lenacapavir, a new antiviral agent, has on the disease. In this week’s Germ Gems post, I discuss the potential impact of lenacapavir and put it in perspective of the WHO’s lofty goal.
Drugs that inhibit HIV replication. There is no vaccine to prevent HIV infection. Since 1987, there have been about 250 HIV vaccine trials all of which failed to show efficacy in preventing HIV infection. Despite the enormously disappointing results of this effort, there
has been recent optimism among researchers that a vaccine is now on the horizon. (See, “After decades of failures, researchers have renewed hopes for an effective HIV vaccine,” NBC News, March 7, 2024.)
In the absence of a vaccine, the main strategy to treat and prevent HIV infection is to administer multiple drugs that target different HIV enzymes the virus uses in its life cycle. To date, the U.S. Food and Drug Administration (FDA) has approved over 30 antiretroviral drugs for the treatment of HIV. These drugs are categorized into six main classes: nucleoside reverse transcriptase inhibitors—the first of these, zidovudine (AZT), was approved in 1988; nucleotide reverse transcriptase inhibitors; non-nucleoside reverse transcriptase inhibitors; protease inhibitors; entry inhibitors; and integrase inhibitors.
A physician specializing in the management of HIV/AIDS guides treatment which usually involves administration of multiple antiretroviral drugs. The rewards of treatment for patients, and for their doctors, include transforming a disease that was uniformly fatal to a chronic condition giving patients a normal lifespan.
In recent years, Pre-Exposure Prophylaxis (PrEP) with one of three FDA-approved drug regimens has become widely recommended for people who are HIV-negative but at high risk of being exposed to HIV through sex or injection drug use. One pill a day of the antiviral Truvada (a combination of emtricitabine and tenofovir disoproxil) is one of the most popular PrEP drugs.
Enter lenacapavir. Gilead Sciences, Inc. is a California-based company that manufactures lenacapavir— a long-lasting inhibitor of the HIV capsid protein that makes use of a unique mechanism of action. By targeting the HIV capsid, lenacapavir interferes with multiple early- to late-stage processes of the viral life cycle. The drug can be administered orally or subcutaneously. In recent randomized control trials, twice-yearly injections of lenacapavir was demonstrated to be superior as a PrEP treatment to once-daily oral Truvada.
The trial designated PURPOSE 1 involved 5,300 cisgender women in South Africa and Uganda who had sex with cisgender men. (Cisgender describes a person whose gender identity aligns with the sex assigned to them at birth.) In this trial, the drug was 100% effective; not a single woman who had received the drug contracted HIV. Following these dramatic findings, the PURPOSE 2 study was conducted across many countries, including the U.S. In this impressive trial, lenacapavir was found to be 96% effective in preventing HIV infection in over 3,200 cisgender men and women.
The finding that twice yearly injections of a drug have high efficacy in preventing HIV lowers the amount of time that an individual has to commit to over their lifetime to protect themselves against infection. This places lenacapavir close to other preventive measures such as vaccines. Many clinical researchers, as well as patient advocacy groups, view the results of these clinical trials as a potential “game-changer.” In recognition of the extraordinary importance of these findings, in 2024, Science Magazine heralded the development of lenacapavir as the “breakthrough of the year.”
But, there is a catch—cost. According to current information, the cost of lenacapavir (sold as Sunlenca) given twice annually is estimated to be over $40,000 per year in the U.S., making it a very expensive option despite its potential effectiveness. Some researchers suggest, however, that with wider production, the price of lenacapavir could drop significantly to around $40 per year per patient.
Other prevention measures. Effective HIV prevention requires a combination of behavioral, biomedical, and structural approaches, including viral suppression, condom use, needle exchange programs, education and policy reform. (See, “Triumphs and threats: HIV in 2024,” The Lancet, November 30, 2024). Securing ongoing funding for these multidisciplinary programs is essential.
The good news is that Gilead has signed deals with six companies in Egypt, India, Pakistan, and the U.S. to sell generic lenacapavir in 120 low-income and lower-middle income countries. (See ibid, The Lancet.) Deals such as this brokered by the pharmaceutical industry, together with ongoing support from the U.S. President’s Emergency Fund for AIDS Relief, now in its 21 st year, support the notion that where there’s a will there’s a way. Perhaps, the WHO’s goal to end HIV/AIDS by 2030 isn’t so farfetched afterall.
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