Hormone therapy appears safe with injectables, but other questions remain

Long-acting injectable medications for HIV treatment and prevention have been an exciting development, offering the option of an every-other-month injection instead of a daily pill. Studies have shown that long-acting injectables are safe and highly effective, and many people view them as a convenient alternative to a pill-based regimen.

But folks in the trans community may have a few more questions in order to consider this option. What do the studies say about these medications for trans folks, and what might they need to keep in mind when considering whether these medications are a good fit?

The injectables

For HIV treatment, the only complete injectable regimen currently available is a two-medication treatment (cabotegravir and rilpivirine, given in two separate shots), which can be given monthly or every other month, brand name Cabenuva. For HIV prevention, the injectable is cabotegravir (brand name Apretude) alone, which can be given every two months.

These medications are safe and effective in general—in studies of the HIV treatment option, fewer than 2% of people had a detectable viral load after taking the medication for 48 weeks. Serious side effects are very rare, although many people do experience mild injection site reactions such as pain or swelling. For PrEP, the cabotegravir injectable was shown to be slightly more effective than the TDF/FTC (Truvada) pill in preventing HIV infection, though both options are highly effective when taken appropriately. 

But are these safe and effective for transgender people? In general, the answer is yes, but let’s look at some considerations about hormone therapy and silicone fillers.

Hormones are safe to take

A major study regarding cabotegravir for HIV prevention included 570 transgender women, 330 of whom were taking estrogen treatment during the study. The study reported similar efficacy in transgender women and cisgender men (which were the only two populations in the study). In a small sub-study, investigators found no difference in drug concentrations between those who were and were not on hormone therapy, suggesting that estrogen treatment does not decrease the effectiveness of cabotegravir for PrEP. There is no specific experimental data currently available for transgender men.

If you’re interested in the injectable, but worried about starting on a long-acting medication that you haven’t tried before, there is the option of taking the same medication in pill form to try it before switching to the injection.

A key study regarding cabotegravir/rilpivirine for HIV treatment reported on participants by sex assigned at birth, and did not separately report data for trans participants; however, expert consensus is that medications like cabotegravir and rilpivirine (which are an integrase inhibitor and a non-nucleoside reverse transcriptase inhibitor, respectively) are unlikely to interact with gender-affirming hormone therapy.

So, while hormone therapy should not be a barrier to trans people who want to use long-acting injectable HIV treatment or PrEP medications, there are some other things to consider.

Other considerations

Specifically, the shot goes in your glute (the muscle of your butt), and it is not currently approved for injection at any other site on the body. This means that if you’ve had silicone injections or other fillers in your booty, this medication probably won’t be an option for you at this time. If you are doing any gluteal intramuscular injections at home (some people inject testosterone intramuscularly), let your provider know about your injection sites and timing.

Keep in mind that you’ll need to receive the injection at your provider’s office every two months within a 7-day window before or after your target injection date. Will you be able to fit more frequent provider visits into your schedule? If you’re currently receiving gender-affirming hormone therapy from a provider different from the provider who manages your HIV treatment or HIV prevention (for example, if you’re seeing an endocrinologist for hormone care and an infectious disease physician for HIV care), would it be possible to reduce some of your visits by finding one provider who can manage both medications? Hormone therapy and PrEP care can both be managed by a primary care provider who is trained to do so, and some HIV specialists or infectious disease providers will manage hormone therapy alongside HIV treatment.

There are some other considerations that aren’t specific to trans folks, but are probably still worth mentioning if you’re considering taking a long-acting injectable for PrEP or for treatment. Many people who struggle with taking a daily pill are excited to switch to cabotegravir/rilpivirine for HIV treatment, but it’s important to know that this treatment is currently only approved for use in those who are already virally suppressed.

Also, the medication isn’t a good fit for people who have liver problems, or individuals who are pregnant or chestfeeding. Since the medication is long-acting, some of it can remain in the body for 12 months after the last injection—someone with a uterus who might be considering a pregnancy for later might want to keep this in mind.

If you’re interested in the injectable, but worried about starting on a long-acting medication that you haven’t tried before, there is the option of taking the same medication in pill form to try it before switching to the injection. The pill form of the medication can also be used if you expect to miss a scheduled shot due to upcoming travel or other reasons.

With these medications, access can be an issue. Some state ADAP programs cover the long-acting injectable HIV treatment, and others do not. For the PrEP injectable, some people have experienced insurance challenges, including high co-pays and difficulty getting approval for coverage of the medication. Fortunately, injectable PrEP has recently received a grade A recommendation from the U.S. Preventive Services Task Force, and will be required to be covered at no cost to patients beginning in 2025.

Dealing with insurance issues can sometimes be extra stressful for trans folks who haven’t changed their name legally or who maintain their health insurance with a sex designation that they no longer identify with. Some community organizations or healthcare facilities may have a case manager or navigator who can help you navigate these insurance issues so that you don’t have to do it all on your own. For people who are uninsured, patient assistance programs may be a potential option to access these medications.


Overall, although it would be useful to have more data about long-acting injectable medications for trans and gender diverse folks, what we do know about these medications suggests that they may be a good option for some who would prefer an injection instead of a pill-based regimen. The injection offers privacy and flexibility, since you don’t have to have pills around for someone to find, or remember to bring them with you if you’re away from home. At the same time, some people don’t mind taking a daily pill (or already take other pills daily anyway) but hate the idea of adding any more doctor visits to their schedule. Since both pills and injectables are safe and effective when taken appropriately, it’s okay to choose based on which will work best for you. 

Finn Schubert, MPH (he, him) is a writer, consultant and former HIV program director living in New York City.