Long-acting injectable (LAI) medications for HIV treatment have much longer half-lives than oral medication, meaning the drug stays at a high enough level in the blood to suppress HIV. Right now, there are three injectable medications approved for treatment of HIV, however, each is used differently:
- cabotegravir and rilpivirine
- lenacapavir
- ibalizumab
Each injectable regimen has its own indications and benefits (and restrictions). People with HIV should consult with their doctors to see whether switching from daily oral meds to any of these injectables would be beneficial.
Cabotegravir + rilpivirine (Cabenuva)
Cabotegravir is an integrase strand transfer inhibitor (INSTI) and is used in combination with rilpivirine, which is an NNRTI (a non-nucleoside reverse transcriptase inhibitor).
In North America and Australia, the injectable combination of these drugs is packaged under the brand name Cabenuva. In Europe, the brand name is Vocabria. Cabotegravir and rilpivirine are administered as two separate injections into the buttock muscles a few minutes apart by a clinician (usually a nurse or doctor). Cabotegravir and rilpivirine (CAB/RPV) can be taken either once a month or every two months. Taking the pill form of these meds for the first month to see if there’s any negative reaction before starting injections is called a “lead in.” It is optional, although most people opt to begin receiving injectable treatment right from the start.
Who can take CAB/RPV?
Injectable cabotegravir and rilpivirine are approved for adults and youth:
- with a viral load under 50 who are already on a stable oral antiretroviral regimen
- without resistance to integrase inhibitors or NNRTIs
CAB/RPV is not, at this time, for:
- people with a detectable viral load
- people who are starting HIV treatment; a person needs to first take an oral antiviral for a few months to achieve an undetectable viral load before switching to an injectable treatment
- children under age 12 (although trials of children under 12 are ongoing)
- people during pregnancy or who are breastfeeding/chestfeeding (though trials for these groups are ongoing)
- people with a strain of HIV called A6
- people with a body mass index over 30 or with buttock implants, which may decrease the ability of the drugs to get into the bloodstream
Injectable cabotegravir and rilpivirine may also have negative reactions for people taking:
- anticonvulsants, including carbamazepine, oxcarbazepine, phenobarbital and phenytoin
- antimycobacterials rifabutin, rifampicin and rifapentine
- the glucocorticoid dexamethasone
- the herbal supplement St. John’s wort
Cabenuva injections are safe for people using gender-affirming hormones, and for people using contraception meds.
Lenacapavir (Sunlenca)
Approved by the FDA in 2022, lenacapavir (LEN) is the longest-acting injectable treatment for HIV, and it’s approved in the U.S., U.K., Canada and the EU under the brand name Sunlenca. Lenacapavir is an HIV capsid inhibitor, which interferes with the HIV capsid, a protein shell that protects HIV’s genetic material, and can be very effective against HIV that has developed resistance to other drug classes. Because lenacapavir stays in the body for a very long time, injections are only done twice a year.
However, LEN must be used in combination with other HIV meds, usually daily pills. This is a difference from cabotegravir+rilpivirine, which is effective as (monthly or bi-monthly) injections alone.
Lenacapavir treatment starts with oral dosing to establish stable blood levels. The recommended oral dose is 600 mg on day 1 and 2, then one 300 mg tablet on day 8. Assuming all goes well, 927 mg may be given via injection on day 15.
Lenacapavir is approved for:
- people who have taken many other HIV meds and have multi-drug resistant HIV and have limited treatment options
- people who are unable to achieve viral suppression on their current regimen
Lenacapavir is not for:
- treatment-naïve people with HIV (people who have never been on HIV meds before)
- pregnant people and children under 18 years (because it hasn’t been studied in these groups)
Lenacapavir is also being evaluated as a first-line treatment and as pre-exposure prophylaxis (PrEP).
Ibalizumab (Trogarzo)
Approved by the FDA in 2018, ibalizumab is a monoclonal antibody given as an injection every other week. Like lenacapavir, it must be taken in combination with other meds. It is for heavily treatment-experienced people whose HIV cannot be treated successfully with other currently available meds.
Who can take Trogarzo?
Trogarzo is for adults with HIV who:
- have taken HIV medications in the past
- have HIV that is resistant to other antiretrovirals
- are failing their current regimens
Trogarzo is not for:
- people with hypersensitivity reactions including infusion-related reactions and anaphylactic reactions
- people who have never been on any HIV treatment.
- children; there aren’t enough data to determine if Trogarzo is safe and effective for kids
Although there aren’t adequate data to determine whether Trogarzo may have risks during pregnancy, other monoclonal antibodies could be transmitted from the pregnant parent to the developing fetus. Based on animal data, infants born to mothers taking Trogarzo during pregnancy could have reversible immunosuppression.
Benefits of long-acting injectables
Based on randomized controlled trials, LAIs for HIV treatment are just as effective as daily pill regimens in bringing the viral load to an undetectable level. A main benefit, in theory, is the ease of adherence, although there are not enough data to conclude this. And it should be noted that in clinical trials, cabotegravir and rilpivirine were given to participants who already had good adherence to daily meds.
People who don’t want a daily reminder of their HIV status, or who want to keep their HIV status private, might benefit from switching to injectable treatments. People who have difficulty swallowing, or who struggle with drug absorption or gastrointestinal issues, may benefit from switching from pills to injectables.
Some considerations
Adherence to an LAI depends on a person’s willingness and ability to make it to their clinic appointments. People who visit their clinic once or twice yearly may find it inconvenient to come in six or 12 times a year. The importance of adherence can’t be overstated. Not taking medication as required can lead to treatment failure and a rise in viral load. People who don’t adhere to a regimen may also develop resistance to the drug types used in the treatment. That includes pills and injectables, but because injections are much less frequent the risk from non-adherence is minimized (though not eliminated).
If a person stops receiving injections and doesn’t switch to another HIV treatment, drug resistance could develop. Fortunately, there is a little bit of flexibility (about one week before and one week after the scheduled injection, for CAB/RPV) for people who are late.
LAI for PrEP
Long-acting injectable cabotegravir (CAB-LA) can also be used for pre-exposure prophylaxis (PrEP), providing another HIV prevention option for people who prefer not taking tablets. Marketed as Apretude, CAB-LA can be used by adults and youth weighing at least 77 pounds as two initial injections that are given one month apart, and then every two months. Individuals can start with a lead-in of oral cabotegravir to see how well they tolerate the drug.
Like daily oral PrEP, CAB-LA does not protect against STIs. In fact, inside and outside of clinical trials, people taking CAB-LA have had high rates of new diagnoses of STIs including syphilis, chlamydia and gonorrhea. Such findings underscore the need for counseling and other sexual and reproductive health services when offering PrEP (either pills or CAB-LA). There is also the small, but significant, risk of developing drug resistance if someone acquires HIV very close to the time of initiating CAB-LA (and therefore still tests negative). Sophisticated (and expensive) diagnostics such as viral load testing could reduce this risk.
Which is better, oral PrEP or CAB-LA? They’re both highly effective in preventing HIV when taken as prescribed. As with LAIs for treatment, the difference comes down to convenience and lifestyle. CAB-LA might help with adherence for people who find daily dosing with pills to be too difficult and would prefer longer-acting meds. The issue of privacy and having to hide medications (this is especially true for people who are unhoused) may make a long-acting injectable preferable for HIV prevention. But they’ll have to make sure trips to the clinic are doable. On the other hand, some people just don’t like getting injections, and for them an oral regimen works best.
The LAI pipeline
There is considerable research by companies trying to develop injectable treatments, whether they be intramuscular, subcutaneous, infusions, or implants, as well as pills that could be paired with LAIs.
Research is underway on:
Weekly islatravir combined with a six-monthly injection of lenacapavir, as well as trials of daily islatravir combined with other pills.
Broadly neutralizing antibodies (bNAbs) for HIV treatment, prevention and long-term viral remission. These include a phase II study pairing a bNAb infusion every two months with a monthly cabotegravir injection. Another trial pairs a bNAB given as an injection every two to four weeks with a fusion inhibitor (albuvirtide) given as a weekly injection. A phase II trial of injectable lenacapavir paired with bNAbs (given as infusions) every 6 months has shown promise.
New medications in development include leronlimab (PRO 140, a CCR5 antagonist which could be given as a weekly injection) and UB-421 (a CD4 attachment inhibitor which could be given as an infusion every two weeks).
The importance of keeping scheduled appointment dates when you’re taking a long-acting injectable medication
- Schedule an appointment date
- You have a window of flexibility from 7 days before to 7 days after your scheduled appointment date
Contact your healthcare provider if you can’t make your scheduled appointment date. Make sure to set up a new appointment within your window of flexibility.