Apretude

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.

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.

Apretude is the first long-lasting injectable PrEP medication—dosed just once a month for 2 months and then every other month thereafter. 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.” The label notes that, “Risk for HIV-1 acquisition includes behavioral, biological, or epidemiologic factors including, but not limited to, condomless sex, past or current STIs, self-identified HIV risk, having sexual partners of unknown HIV-1 viremic status, or sexual activity in a high prevalence area or network.” Advice on preparing for injection site reactions is included along with the risk of developing drug resistance 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 does not prevent or treat hepatitis B. 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.

Dr. Melanie Thompson:

In clinical trials, Apretude was superior to oral Truvada in preventing new HIV infections among gay and bisexual men and transgender women, and among cisgender women. Injection site reactions were very common but rarely caused anyone to stop taking the drug. It is important to test for HIV before each dose of CAB because missing an acute HIV infection while on CAB as PrEP could result in cross-resistance to all integrase inhibitors and limit treatment options. Currently, CDC recommends an HIV RNA viral load test before every dose, but this may change, so consult guidelines frequently. CAB levels decline after 2 months to the point that it can’t prevent HIV but may be associated with drug resistance for people who acquire HIV after taking the drug. Modeling studies suggest that low levels of CAB may persist for up to three or four years (especially in ciswomen), thus heightening concerns about viral resistance. As a result, an INSTI genotype is recommended for anyone who acquires HIV after exposure to CAB PrEP. If it is important to begin HIV treatment before the genotype result is available (such as in the setting of acute infection), HHS and IAS-USA guidelines recommend beginning with a boosted darunavir regimen (Prezcobix + TDF or TAF and FTC or 3TC, or Symtuza). This could be changed to an INSTI-based regimen if no resistance is found, in order to avoid drug interactions with cobicistat. Long-acting CAB for PrEP could be a major advance in our ability to end the HIV epidemic, if only it can be broadly accessible to the most heavily impacted groups, especially Black and Hispanic/Latino populations. A great deal of public and provider education is needed, and the high cost of the drug as well as the operational logistics of administration are significant obstacles.

Activist Joey Wynn:

This revolutionary formulation will have a huge impact in dramatically reducing new cases of HIV domestically. Barriers removed can include the burden of taking pills and going to the pharmacy every month for pick up, co-pay costs, and all the other headaches of getting and taking pills, as well as the stigma some people experience seeing HIV medicine bottles in the home.  Now hopefully, we’ll get to see a majority of folks staying on their PrEP year round. The biggest barriers are insurance plan coverage and distribution access, particularly in the northeast. Let’s get some advocacy going to iron out these distribution problems so people can get what they need in all the injectables as a class.