Someone walks into a clinic or the office of their care provider asking about a long-acting injectable, a new mode for HIV prevention or for treatment of their HIV. What happens next?
Instead of a daily pill, long-acting injectables (LAIs) are miedications administered by injection that can remain effective for months. LAIs are not only a game changer, they are a whole new game in the fight against HIV. There are new players, new rules and new requirements.
Cabotegravir was approved in December 2021 by the U.S. Food and Drug Administration as the first long-acting injectable for PrEP. Known by its brand name, Apretude, it is initially administered as a monthly shot for the first two months, and then as a single injection every two months. Before starting the injections, there’s an optional pill version of cabotegravir that can be taken, although testing has shown this oral lead-in is not necessary.
For HIV treatment, cabotegravir is combined with another HIV drug, rilpivirine. Known as Cabenuva, it is the only complete treatment regimen in LAI form. Two shots of the combo are administered (one in each butt muscle) every two months, with an optional one-month oral lead-in.
Another long-acting injectable, lenacapavir, marketed under the name Sunlenca, is administered to the abdomen every six months, but daily oral antiretroviral medications must still be taken.
Located on the second floor of the Strut building in the Castro, Magnet is operated by the San Francisco AIDS Foundation in close collaboration with the city’s department of public health. It is one of San Francisco’s busiest sexual health clinics, providing PrEP to about 3,000 people—50 to 60 of whom are on long-acting injectable PrEP, says Hyman Scott, MD, MPH, Magnet’s medical director. (Dr. Scott is also an infectious disease physician at Zuckerberg San Francisco General Hospital’s Ward 86 HIV/AIDS clinic.)
What happens when someone asks about LAIs?
“If someone is interested in long-acting injectable PrEP, we do education about what it is, how it works, what the requirements are for getting started,” Dr. Scott says. “And then there’s quite a bit of insurance navigation that’s required for long-acting injectables that is more intensive compared to oral PrEP.”
Testing is key to LAIs, whether for HIV prevention or treatment. People receiving cabotegravir for PrEP are given an HIV viral load test every time they receive an injection. That’s because if a person has acquired HIV, it will be detected more quickly by a viral load test (which measures how much virus is in a person’s blood) than an antibody antigen test, which detects the immune system’s response to HIV exposure.
‘My advice is always, make it as simple and as streamlined as possible. That’ll be the best thing for our patients, but also for us as care providers.’
Viral load tests are also checked for people receiving LAI for HIV treatment, but usually not at every injection.
In both instances, the point is to make sure that the individual is responding to their LAI and to get ahead of any acquisition of the virus or the virus developing resistance to the medication.
“If someone has delays or misses injections, we might be testing more frequently,” Dr. Scott says. “We just want to be careful and make sure that if there’s a problem, we identify it as early as possible.”
The two-month injection schedule for long-acting PrEP does have some flexibility.
“There’s about four weeks after the target date that we have to get someone in for their injections without them having to restart, without the extra reloading injection,” he says. “We want to make sure that the levels of the medication for prevention stay high enough to keep someone protected. If it’s more than four weeks after the target date, we have concerns that the levels have dropped such that someone may not have high enough protection.”
If the client is not able to make it within the four-week window, they can be given oral medication until the next scheduled shot, Dr. Scott says. He adds that a client can receive their injection one week early if needed.
The main side effect has been pain and tenderness around the injection site lasting about two days, he says, which can be treated with ibuprofen or Tylenol if necessary. General fatigue and achiness can also occur, and usually goes away after a couple of days.
“I tell most people who are starting a long-acting injectable, Yeah, this is gonna hurt your butt cheek for a couple of days,” he says. “And it’s not something that’s generally immediate. There’s a little bit of inflammation response—that generally happens like the evening of or the next day.”
This new mode of treatment means many care providers, clinics and other facilities that administer LAIs need to rethink how they work.
“There’s a new level of patient management that is required for injectables that is not as necessary for oral PrEP,” he says. Some clinics have worked with infusion centers and pharmacies to offer patients more options and locations.
“My advice is always, make it as simple and as streamlined as possible,” Dr. Scott says. “That’ll be the best thing for our patients, but also for us as care providers. Oral lead-in, for example, is something that should be offered to individuals who want it, but it’s not strictly necessary. Offering direct-to-inject and making testing as easy as possible for individuals is also really important.”
For care providers and their practices, there are major differences between long-acting injectables and oral medications.
“Insurance was the biggest surprise for me,” he says. “I thought we had figured out a lot of the things for getting people onto PrEP for the last 10 years, but this is a whole new game.”
Scott’s Magnet clinic has staff who have become experts in getting insurance approval for LAIs. “Our navigation team says they can eventually get it for everyone, but sometimes it can take four to six weeks, or even eight weeks for them to get through all the insurance hurdles that are put up for people who are privately insured as opposed to oral PrEP, where we can get access within 24 to 48 hours,” he says. Insurance companies have also pushed back against injectable PrEP because of the availability of a generic version of oral PrEP (a combination of tenofovir DF and emtricitabine), he adds.
People on public health insurance such as Medicare or Medicaid (known as Medi-Cal in California) have a much easier time getting onto long-acting injectable PrEP because of government policies and laws supporting PrEP access.
“We talk a lot about starting PrEP, but staying on PrEP is also very important,” he says. “When people stop, for whatever reason, it’s often because of the hassle of staying on it—insurance, visits, testing costs. We have to remove the hassle factor from our implementation—at a policy level, a clinic level, a provider level.”
With their challenges and potential for change, how will LAIs affect accessibility and inequities in healthcare?
“I don’t think we know overall yet, whether or not they make inequities worse,” Dr. Scott says. “I think they have the potential to close some of the inequities that we see. My concern is that it depends on systems, clinical systems, and we know that those systems are not equitable. We’ve seen inequities worsen with oral PrEP. In clinical studies, we saw a very high efficacy among Black men who have sex with men and with transgender women on injectable PrEP. [LAIs] are a really powerful tool that can change the trajectory of the HIV epidemic in the United States. Oral PrEP was transformative, and I think this long-acting injectable option is also transformative. But we can’t leave Black people behind, we can’t leave Latinx people behind.
“The prevention tool itself is necessary, but not sufficient. What we need is to ensure that we have all of our systems in place to make sure that these tools are used in ways that can most benefit our communities. We know where the gaps are. The research has been clear about where we are and I think there’s consensus about where we need to go. The challenge is how do we make that happen. What does it take to achieve those goals? Long-acting cabotegravir gives us an opportunity to think about some of the transformations that are necessary, because it takes a little bit more work to implement them. The data will tell us whether we’re doing it or not. We will have an answer, and I just hope it’s a different answer than we’ve had in the last 10 years for oral PrEP.”
Working toward those transformations, Dr. Scott feels a personal connection.
“It’s joyful to work with clients and patients; it’s recharging in many ways,” he says. “I love the connection with community, with my patients, with the work.
I went into HIV because of the absolute connection between the community affected by HIV and the medical community. I haven’t seen that type of a connection in many other places or with other conditions; it is a tremendous opportunity and privilege for me to be part of these communities.”