The Many Options of Preventing HIV with PrEP
From daily pills to long-acting injectables, advances in scientific discovery address people’s diverse needs with a range of choices to stop HIV infection
By Andrea Gramatica, PhD
When we talk about pre-exposure prophylaxis in general, we’re referring to approaches that prevent the spread of a disease in individuals who have not yet been exposed to whatever agent causes it. Vaccinations are the most commonly used form of pre-exposure prophylaxis: They prepare our immune system to recognize and fight a pathogen before the pathogen has infected us. But when we talk about pre-exposure prophylaxis, or PrEP, in HIV, we are not talking about a vaccine or a cure. We are referring to the use of antiretroviral medications to prevent HIV from establishing an infection when someone is exposed to the virus.
The era of PrEP begins
The first generation of PrEP for HIV was approved by the FDA in 2012. It was based on two antiretroviral drugs used to treat HIV taken together in a single daily tablet. Initially distributed under the brand name Truvada, this first PrEP regimen has been available also as a generic medication for the past six years.
Seven years after Truvada, another daily option, Descovy, was approved for preventing HIV transmission through sexual activity. Descovy has also proven to be effective.
Taking Truvada or Descovy every day is discreet and convenient, but not every person is able to stick to a daily regimen, and these medicines only work if they are taken consistently. People may miss doses or stop PrEP because of difficulty obtaining prescriptions, stigma, privacy concerns, or simply the burden of taking a medication every day.
Injectable PrEP introduced
For more than a decade, PrEP largely meant taking a pill every day, and, while this regimen remains extremely safe and effective (if taken consistently), it is no longer the only option available. Now, we have two injectable medicines (cabotegravir and lenacapavir) that can be administered less frequently while providing protection for months at a time.
Cabotegravir (brand name Apretude) was the first long-acting PrEP approved by the FDA in 2021. This medication is taken every two months and can be used by people for whom risk of kidney disease makes oral PrEP (like Truvada or Descovy) unsuitable. However, these injections must be administered by a healthcare provider, so keeping appointments becomes the new form of adherence. Researchers are also studying an extra-long-acting formulation of cabotegravir that could potentially extend injections from every two months to every four months, but this approach is still in the early stages of development.
The landscape changed again in June of 2025, when the FDA approved lenacapavir (Yeztugo) for PrEP. After a start-up dose, lenacapavir is administered as under-the-skin injections just twice a year. Early clinical trial results were remarkable, and lenacapavir immediately became the new hope to remove much of the day-to-day burden associated with HIV prevention. However, people still need regular HIV testing and must return on schedule for their next injections.
The future of PrEP
Additional research pipelines continue to move toward less frequent dosing: A new experimental once-a-month drug, alimatravir, is currently in Phase 3 clinical trials, being tested in a large group of people. If successful, alimatravir could offer something between the daily pill and injection options.
Another important consideration is that prevention strategies can and should be designed around different preferences, circumstances, and needs. For example, several topical PrEP options are currently being tested, such as rectal/vaginal gels or vaginal rings. So far, however, only one has been clinically approved and only in some African countries.
In conclusion, there is no single “best” form of PrEP. For one person, taking a pill every day may be far easier than visiting a clinic for an injection. For someone else, eliminating a daily reminder of HIV risk may make a monthly or twice-yearly PrEP option transformative. The only “best” form of PrEP is the one that is available to everyone: The challenge remains to ensure reliable supplies, functional healthcare infrastructures, and affordability. Without access, the promise of these new PrEP regimens matters little if the people who could benefit from the HIV prevention option cannot obtain it.
Andrea Gramatica, PhD, is amfAR’s VP of research.
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