Aaron Siegler, PhD, is a professor of epidemiology at Emory University’s Rollins School of Public Health and lead investigator of PrEP Locator. Siegler’s infectious disease research focuses on public health impact through implementation science and clinical trials.
HIV prevention has entered a new era, with a growing number of approved and emerging PrEP (pre-exposure prophylaxis) options extending beyond the traditional daily oral pill regimen.
Cabotegravir (brand name Apretude) is a long-acting injectable option for PrEP approved to reduce the risk of sexually acquired HIV infection in people at high risk of infection, including men who have sex with men as well as women and transgender women who have sex with men. The drug was developed by ViiV Healthcare, the global specialist HIV company majority owned by GSK, and received regulatory approval in late 2021.
Public health experts see tremendous potential in the expanding range of PrEP options to help change the course of the HIV epidemic, but questions remain about whether enough people who could benefit from the drug will take it.
“People can choose what fits their life best, and I think that’s the real power,” says Siegler.
We spoke to Siegler about cabotegravir, how this medication works, and what sets it apart. The interview was edited for length and clarity.
Q: Who typically benefits from this treatment?
Siegler: There is no indication-specific guidance around who would benefit from one form of PrEP versus another, but in general, persons who might have a hard time taking daily pills for whatever reason, whether it's simply a matter of logistics in their life, a matter of stigma, or any other issue, injectable PrEP is a really good fit for folks who would struggle with taking their medication.
Honestly, I really think we're entering a new era of choice, and with that choice, it's really about what an individual would prefer and be most likely to sustain over time, because HIV risk accrues over time. The key is not to be on a medication for a really short period, but instead to have a sustained period of protection.
We know certain groups are at a higher risk for HIV infection, including men who have sex with men and people who inject drugs. Black men who have sex with men face by far the highest levels of HIV prevalence and incidence of any group in the United States, a disparity shaped by historical and structural factors, including inequities in access to care and treatment.
These individuals and others who might be at risk for HIV infection should talk to their healthcare providers about their personal risk and whether PrEP might be right for them, since PrEP is a highly effective tool for preventing HIV.
Q: What sets this treatment apart from others?
Siegler: The biggest difference is how this medication is administered and how often it needs to be administered. Unlike oral PrEP options taken as pills, cabotegravir is an injectable medication that is administered every two months.
It is given as an intramuscular injection, which means the shot goes deep into the muscles.
Another new PrEP injection (lenacapavir) is administered subcutaneously, meaning it is injected just under the skin, and is administered twice a y
ear.
Q: How well does this treatment work?
Siegler: Every PrEP modality is highly efficacious. Each one, if taken as prescribed, lowers the risk of getting HIV from sex by over 99%. So it really comes down to adherence. Note: There is limited data on the use of cabotegravir for HIV prevention among people who inject drugs. However, clinical trials of PrEP pills show PrEP can substantially reduce the risk of HIV infection among people who inject drugs when taken as prescribed.
There are clinical trials showing that injectable PrEP performed much, much better than oral PrEP, but that’s an adherence issue. The medication itself is protective. It is extraordinarily protective. An injectable just fundamentally provides longer-lasting coverage, which makes it more protective than pills that may be taken imperfectly. As we saw in clinical trials, the effect was substantial. These weren't small improvements relative to daily oral PrEP. They were major benefits for population health.
At a population level, if we can get a greater proportion of people at higher risk onto injectable PrEP, we will see better outcomes because we know some people fundamentally have trouble taking pills. A lot of people do. It's just hard.
I like to think through who's taking these medications. These are sexually active people, often young, healthy. Many of them don't have experience taking other kinds of medications on a regular basis. Most PrEP users are male, and fundamentally, males very rarely seek prevention care.
In that framework, you start to understand why injectable PrEP is important. You have a group of young, healthy people who are not used to taking daily pills and aren’t used to worrying a lot about their health. Having something that’s essentially “set it and forget it” is empowering.
Q: Is this treatment generally considered safe?
Siegler: It's incredibly safe. There is a really important body of research on all of these antiretroviral medications that are generally well tolerated and have been around for a really long time and have been studied pretty extensively. Because of that, we have a strong understanding of their safety profile.
One paper even compared the side effects of daily oral PrEP with those of aspirin and concluded that daily oral PrEP had a slightly more favorable side effect profile. So that's the level of safety we're talking about with these medications. The risks are minimal especially when weighed against the substantial benefits these medications provide.
The safety profile of cabotegravir is very similar to the oral pills. The main difference is less about overall safety and more about side effects.
Q: What sort of side effects can people expect, and are there ways to handle them?
Siegler: Some people experience injection site discomfort, maybe injection site pain, a little bit of swelling or redness, maybe some bruising, which is the most common side effect associated with both injectable PrEP medications.
Other common side effects include headache, nausea, and diarrhea. Most are mild and improve within a few days and can be managed with over-the-counter medication.
Q: How do you take this treatment, and will people need any regular tests or checkups?
Siegler: Cabotegravir must be prescribed by a clinician and administered in an appropriate clinical setting.
Before starting any PrEP medication, people are tested for HIV to confirm they do not have HIV. Because people at risk for HIV are often also at risk for other sexually transmitted infections, or STIs, testing for STIs is generally recommended. This testing typically includes screening for syphilis, chlamydia, and gonorrhea.
Q: Are there any types of people who shouldn’t take this treatment, like those with certain health conditions or who are taking other medications?
Siegler: Generally speaking, no. Most people can take these medications. And there aren’t any large groups who are automatically excluded. There may be some situations where a doctor may want to take a closer look such as some liver-related concerns, or those taking medications that may need additional monitoring. There are also minimum weight requirements of 77 pounds.
In most cases, these are not absolute contraindications, but factors that patients and their clinicians should discuss when weighing the benefits and the risks.
Q: How much does this treatment cost? Is the list price really several thousand dollars a year? Will insurance cover it, or are there options for financial assistance?
Siegler: Cost is definitely an issue, but it shouldn’t prevent someone from considering PrEP. Medicaid and Medicare currently cover it very well. And most private insurance plans are required to cover both oral and injectable PrEP under the Affordable Care Act. For private insurance, coverage can often require coordination and going back and forth between the provider and insurer.
Usually the cost wouldn’t fall on the individual in the end. I think anyone interested in PrEP should talk to their doctor and figure out how they can get on PrEP at no cost to them.
Q: Can you give some insights into the research and studies behind this treatment?
Siegler: For cabotegravir, there is something called the HIV Prevention Trials Network, and it's a collaborative clinical trials network that conducts large-scale trials of often new medications, and in this case, there was a large clinical trial where there were several large clinical trials that had different populations in each trial, but they all had relatively similar findings.
The studies compared injectable cabotegravir to standard of care, which was daily oral PrEP, and in every case, the injectable medication was found to be superior in efficacy to daily oral PrEP.
Q: How can people find out more about whether this treatment would be a good fit for them?
Siegler: The first thing I’d say is these medications can provide incredible peace of mind. There's a real benefit to knowing, ‘I am protected. I don't have to worry. I can live my life, and without fear.’
Traditionally, antiretroviral medications, or ARVs, were the domain of HIV specialists. When PrEP was approved, however, all of a sudden there is this medication that is supposed to be prescribed by primary care doctors. It's a medication that comes with its own set of labs and clinical management. It's not especially complex, but it's not the bread and butter of every primary care doctor.
Primary care doctors tend to have areas where they feel most comfortable, and some may have limited experience with PrEP and many may be less familiar with newer options like a long-lasting injectable PrEP.
Many people prefer to see a doctor who's very experienced in prescribing PrEP. That’s one reason we created the PrEP Locator in 2016. At the time, there was no national resource that made it easy to find a PrEP provider. More recently we’ve expanded the service to help people find clinicians who offer injectable PrEP as well.
