Modern antiretroviral therapy (ART) — the term for HIV treatment regimens — has come a long way over the past four decades. Now, many people live longer, full lives with well-controlled HIV without developing AIDS. However, for some people, ART has drawbacks.

Most therapies come in pill form, which poses problems for people who have trouble taking them. Additionally, all oral ART must be taken daily — sometimes, multiple times per day — and remembering to take the medication can be challenging. In a 2021 retrospective study of more than 200,000 people with HIV in the U.S., researchers found 60 percent didn’t take their medicine regularly enough. Even more concerning, 42 percent had very poor adherence, meaning they took less than 80 percent of their prescribed doses.

New injectable therapies are promising, long-lasting alternatives that don’t require daily administration. In this article, we’ll look at some of the newer injectable treatments for HIV and how they compare to oral treatments.

Injectable Medication for HIV Treatment

In January 2021, the U.S. Food and Drug Administration (FDA) approved an HIV treatment called Cabenuva. Cabenuva is a combination of cabotegravir and rilpivirine — both extended-release injectable medications. It’s the first injectable treatment for HIV approved by the FDA.

Cabotegravir and rilpivirine lead to viral suppression in someone living with HIV, but in different ways. Cabotegravir is an integrase inhibitor. This means it stops the integrase protein, thereby preventing the virus from integrating into the human DNA and then making more copies of HIV.

Rilpivirine is an HIV nonnucleoside reverse transcriptase inhibitor (NNRTI). Drugs in this class stop an HIV protein called reverse transcriptase. Reverse transcriptase is also necessary for HIV to make copies of itself, and NNRTIs prevent this from occurring.

Cabenuva is designed to be administered once per month as an intramuscular injection, which means it goes into the muscle of the buttocks. If the monthly injections are working well, sometimes switching to one dose every two months is an option.

Cabenuva is designed to replace the current ART regimen of daily pills for people with well-controlled and stable HIV. People who have well-controlled HIV are considered virologically suppressed or “undetectable.” A person is considered to have well-controlled HIV — and be a possible candidate for Cabenuva — if their viral load (HIV levels in the blood) is less than 50 copies per milliliter for three to six months. People who receive Cabenuva should also have no known drug resistance to either cabotegravir or rilpivirine.

It’s important for anyone taking Cabenuva to get their injections on time to help prevent developing drug-resistant HIV.

Before starting injectable Cabenuva, you may have the option to take the oral formulations of cabotegravir (Vocabria) and rilpivirine (Edurant) for one month. This practice is called oral tablet lead-in. Taking the oral tablets first can establish how well you would tolerate these medications and determine if you would experience any side effects.

The extended-release cabotegravir component of Cabenuva can remain in the body for up to 12 months. If the oral tablet lead-in goes well, you should be able to start monthly injections of Cabenuva. If you plan to miss an injection by more than seven days, you can take cabotegravir and rilpivirine orally until the next injection of Cabenuva. Missing or taking very late doses of Cabenuva can result in resistance to both cabotegravir and rilpivirine. Ask your doctor what approach would be best for you.

Injectable Medications for HIV Prevention

In December 2021, the FDA approved Apretude — an extended-release injectable formulation of cabotegravir — as a preventive treatment for adolescents and adults who are HIV-negative but at risk of being infected by HIV. Preventive medication given before possible exposure to HIV is called preexposure prophylaxis (PrEP).

Apretude is initially administered as an injection into the buttocks once a month for two months, then every two months after that. You must have a documented negative HIV test before starting Apretude.

In 2025, the FDA approved Yeztugo (lenacapavir), which is given as a twice-yearly injection to prevent sexually acquired HIV-1. Yeztugo is indicated for adults and adolescents who are HIV-negative and at risk of infection. The medicine works by blocking a viral capsid (a protective shell) that HIV needs to make copies of itself. Treatment starts with a two-day setup: two oral tablets and one injection. After that, people receive two injections under the skin every six months.

In phase 3 clinical trials, nearly 100 percent of participants remained HIV-negative on Yeztugo.

Like other PrEP options, Yeztugo requires a negative HIV test before each dose. Because it stays in the body for up to a year, it’s especially important to keep up with scheduled injections to avoid developing drug-resistant HIV.

Benefits of Extended-Release Injectables

Sticking to ART or PrEP medicines can be difficult because the pills must be taken at least once daily to control or prevent HIV infection. Sometimes treatment requires several different pills or requires you to take pills many times per day. An online survey by the pharmaceutical company ViiV found that people struggle with daily pills due to emotional challenges like anxiety about missed or late doses and because of privacy concerns about others discovering their HIV status.

Although injections can be painful and require administration by a nurse, Cabenuva and Apretude are only administered every one to two months. Research has shown that people who have difficulty adhering to an oral-medication regimen are more likely to stick to their treatment plan if they switch to long-acting injectables.

More recent research suggests that people who had difficulty sticking to a daily regimen of oral ART may be more likely to achieve viral suppression if they switch to long-acting ART. However, further studies are needed to confirm this.

Cabenuva is just as effective at treating HIV as the oral pill alternatives cabotegravir and rilpivirine. In clinical trials, a higher percentage of participants receiving the injectable therapy maintained well-controlled HIV by the end of each clinical trial, compared to those taking the pills.

In a study with cisgender men and transgender women who have sex with men, long-acting injectable Apretude administered as PrEP was found to be more effective at preventing HIV than emtricitabine/tenofovir disoproxil fumarate (Truvada), a once-daily pill used for PrEP. Although both the oral and injectable drugs were considered “highly effective,” the study authors concluded Apretude was even more effective because it was easier to take consistently.

In clinical trials to date, researchers have found injectable cabotegravir taken either every month or every two months to be well tolerated. Mild injection-site reactions were the most common side effect.

A possible downside to taking injectable Apretude for PrEP is that a person can acquire drug resistance to medications within the integrase inhibitor class. If a person does acquire HIV while taking injectable PrEP with cabotegravir, then treating the HIV may be more difficult.

People starting PrEP with this medicine must be well screened for HIV at the start of therapy, one month into treatment, and then at least every two months while on treatment. If a person waits longer than two months after their most recent injection, they must switch to oral PrEP treatment and/or use condoms or abstinence consistently to avoid developing an HIV infection that is resistant to the integrase class of medicines.

Injectables for Those Who Are Resistant to Other HIV Medications

In addition to the two medications mentioned above, the FDA has approved injectable treatments intended for people who are resistant to other HIV medications. They include a formulation of lenacapavir called Sunlenca and a formulation of ibalizumab-uiyk called Trogarzo. Keep in mind that both of these drugs need to be taken alongside other HIV medications — most often, daily pills — to be effective. This offsets one of the key benefits of taking just one extended-release injectable.

Sunlenca is an HIV capsid inhibitor, approved by the FDA in December 2022. It works by disrupting the assembly and disassembly of HIV capsid (the protein shell of a virus), thereby preventing the virus from infecting cells and forming new viruses. Initially, you’ll need to take an oral version of the drug for up to a week. Taking the oral form helps ensure you can tolerate it. From there, though, only two injections are required per year.

Trogarzo is a laboratory-engineered antibody that specifically targets the CD4 receptor on T cells, a key entry point for HIV to infect these cells. The drug prevents HIV from attaching to and entering T cells, thereby blocking the infection process at a critical stage.

Ibalizumab was first approved in 2018 for administration via an IV infusion, starting with a single loading dose (an initial high dose) followed by additional doses every two weeks. The FDA approved a new version of the drug in October 2022. It’s also delivered via an IV every two weeks, but the infusion takes 30 seconds instead of 15 minutes.

Side Effects of Injectables

Researchers have observed some side effects from these injectables, some of which they share in common and some of which are unique to each individual drug.

Common Side Effects

Common side effects for all four medications include injection site reactions, which can include pain and swelling. Nausea and rash are also commonly reported for these treatments.

More severe but less common side effects shared among these treatments include hypersensitivity reactions, which may manifest as severe rash, fever, or difficulty breathing.

Drug-Specific Side Effects

Uncommon but possible side effects for Cabenuva include fatigue, fever, nausea, depression, and muscle or bone pain. Liver toxicity (damage to the liver) can occur, especially in people previously diagnosed with hepatitis B or hepatitis C.

Rare but serious side effects of Apretude include the risk of drug resistance when it’s used for HIV-1 PrEP by someone with an undiagnosed HIV-1 infection. Other side effects listed on the drug’s label include gas, stomach pain, vomiting, muscle pain, decreased appetite, depression, drowsiness, back pain, and upper respiratory tract infection.

Sunlenca’s prescribing information warns that the drug could remain in a person’s system for 12 months or longer, potentially affecting how the body absorbs and processes other drugs. As with any new medication, a doctor or pharmacist would need to check for any drug interactions.

Trogarzo’s side effects may include diarrhea, dizziness, nausea, and rash. These side effects were all listed as mild to moderate in the studies for drug approval.

For Cabenuva, Apretude, Sunlenca, and Trogarzo, there haven’t been enough studies on the use of these medications during pregnancy to adequately assess a risk of birth defects and miscarriage. If you have questions regarding pregnancy or breastfeeding and these medications, ask your doctor.

Talk With Others Who Understand

On myHIVteam, the social support network for those diagnosed with HIV, you can connect with others. Members come together to ask questions, give advice, and share their stories with others who understand.

Are you interested in injectables for HIV treatment? Have you tried them? Share your insights in the comments below, or start a conversation by posting on myHIVteam.