Apretude
Daily oral lead-in therapy for about a month to determine tolerability is optional before injections begin, consisting of a 30 mg tablet of Vocabria. Initiate injections on the last day of oral lead-in. Individuals who were on daily oral PrEP with Descovy or Truvada can transition directly to Apretude injections once their HIV-negative status is confirmed. If up to 8 weeks of treatment is missed (less than or equal to 2 months), restart injections with the 600 mg dose of CAB-LA as soon as possible, and then dose every 2 months thereafter. If more than 8 weeks of therapy have been missed, restart treatment with a 600 mg dose as soon as possible, followed a month later with another 600 mg dose, and then dose every two months thereafter. The oral medication can also be used as “bridging” if shots cannot be obtained on time—see package insert for instructions on planned and unplanned missed injections. The effect of severe liver impairment on cabotegravir is unknown. A longer two-inch needle (not included in the dosing kit), may be required for people with a higher BMI (body mass index) of 30 or more. Do not administer Apretude injections at any site other than gluteal muscle because the effects of drug absorption at other sites is unknown. At this time, injections should only be administered by a healthcare professional.
- Oral cabotegravir is not available unless being prescribed cabotegravir-LA.
- See package insert for more complete information on potential side effects and interactions.
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JO-ANN JOSE, MD, MPH:
Two high-profile clinical studies of cabotegravir for PrEP—HPTN 083 and HPTN 084—found cabotegravir for PrEP (Apretude) highly effective in diverse populations. It is an injectable given once every two months. There is some inconvenience associated with that. You have to come into the doctor’s office to get the injection there. This is not a self-injection product, but that also means that adherence is directly observed. It is a game changer for PrEP, especially for cisgender women. It represents a great leap forward for prevention. There is no question that this is a great PrEP drug and it works really well; the next question is about making it accessible to more people. This is a very expensive drug and insurance protocols for accessing Apretude are complex. A clinic that has experience with long-acting injectables will be most helpful to address the barriers to access. Because cabotegravir has a long half-life, the drug can stay in your body for months or even longer after you stop receiving it—this is called a long PK tail [PK, or pharmacokinetic, relates to how drugs move in your body]. If there’s imperfect adherence, it is possible that someone could acquire HIV while cabotegravir is still in their system, and therefore their HIV could develop resistance mutations to the drug, known as LEVI (Long-Acting Early Viral Inhibition) syndrome, which is a much bigger concern. That’s because most first-line HIV regimens, both in the U.S. and globally, use an integrase inhibitor backbone. If resistance develops, that person could lose access to an entire class of highly effective and well-tolerated HIV medications. For someone who was previously on cabotegravir for PrEP and has acquired HIV, the recommendation is to avoid integrase-based treatment regimens and use a protease inhibitor-based regimen with darunavir instead. When people with LEVI syndrome were given a standard fourth-generation HIV test, they did not always test positive. Later on, they were found to be positive by using other means, usually an HIV RNA test. And then when they went back and looked at stored samples, they discovered that an earlier testing with an RNA test would have discovered HIV acquisition earlier. That’s why current PrEP guidelines now recommend that people on PrEP—especially anyone on cabotegravir—receive both a standard HIV screening test and an RNA test to ensure HIV acquisition is caught as early as possible.
Cabotegravir cannot be taken with rifampicin, rifapentine, carbamazepine, eslicarbazepine, oxcarbazepine, phenytoin, phenobarbital or St. John’s wort. It is recommended to co-administer rifabutin with caution because rifabutin can moderately increase the metabolism of cabotegravir and result in lower protective levels of cabotegravir. The effect of feminizing medications and hormones is not known. Methadone dose may need to be adjusted. Antacids should be taken at least 2 hours before or 4 hours after oral cabotegravir. Tell your provider or pharmacist about all medications, herbals, and supplements you are taking or thinking of taking, prescribed or not, as there are other drug interactions that are not listed here.
Optional oral lead-in can be used to assess for safety and tolerability, especially in individuals who have a history of rash, allergies or severe intolerances to past medications. The most common adverse reactions observed in 4% or more of people in clinical trials were injection site reactions (84%, with 59% having at least Grade 2—moderate—reactions), pyrexia (includes feeling hot, chills, and flu-like symptoms), fatigue, headache, and diarrhea. Hepatotoxicity has been reported in people with and without previous known liver problems or risk factors. Depressive disorders have been reported with Apretude and should be monitored. People given injections should be observed for approximately 10 minutes afterwards to monitor for potential reactions. Individuals with pain from injections can use an ice pack or heating pack, and are advised to stretch and remain active. It is not recommended to overly massage the area. Monitor for signs of hypersensitivity, including elevated liver transaminases, and treat as needed.
Individuals should be tested for HIV infection before receiving every injection. Updated guidelines recommend HIV negative test results should be confirmed with a negative HIV viral load test as well. According to PrEP guidelines from the U.S. Centers for Disease Control and Prevention (CDC), “Cabotegravir injections may be especially appropriate for people with significant renal disease, those who have had difficulty with adherent use of oral PrEP, and those who prefer injections every 2 months to an oral PrEP dosing schedule.” Advice on preparing for injection site reactions is included along with the risk of developing drug resistance if HIV is acquired after stopping medication and the drug is still leaving the body, and the importance of keeping up follow-up appointments if stopping PrEP for any reason. For individuals who want to discontinue Apretude but who also have ongoing risk of sexual and injection HIV exposure, guidelines recommend these individuals be provided another highly effective HIV prevention method following their last injection. HHS guidelines have a section on the use of cabotegravir-LA for people with a history of injection drug use. Apretude is not recommended for people who are pregnant. Because cabotegravir-LA has been detected in systemic circulation for up to 4 years or longer after the last injection, consideration should be given to potential for fetal exposure if prescribing cabotegravir to people of child-bearing potential who are not on birth control. Pregnant individuals can voluntarily enroll in the Antiretroviral Pregnancy Registry through their provider; GO TO apregistry.com.
JUAN MICHAEL PORTER II:
Apretude is preferred by many people who’ve switched to it because they no longer have to worry about taking a daily pill or missing a dose. It is incredibly effective for people of all backgrounds. In the U.S., the only case of failure occurred with a gay man who was having more extreme versions of sex in combination with substance use. The major barrier to access is cost. But knowing that a drug that is used is more effective than one that isn’t should erase that consideration out of hand.