Apretude

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, oxcarbazepine, phenytoin, and phenobarbital. 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. New options are highly desirable—different strokes for different folks. 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 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. DHHS 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 12 months 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 for cisgender women. Injection site reactions were very common but rarely caused anyone to stop taking the drug. Because the risk of missing an acute HIV infection when starting CAB PrEP could result in cross-resistance to all integrase inhibitors and limit treatment options, an HIV RNA viral load test is required before every dose of CAB. 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, 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), DHHS 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. In spite of concerns about drug resistance, 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 populations. This is a heavy lift. A great deal of public and provider education is needed, and the high cost of the drug (wholesale acquisition cost of $3,700 per dose) as well as the operational logistics of administration, are significant obstacles. Currently, oral PrEP must be provided to insured persons without out-of-pocket costs due to its “A” rating from the U.S. Preventive Services Task Force (USPSTF). At the time of publication, USPSTF was in the process of updating its recommendations to include CAB PrEP. To facilitate uptake with equity, the drug as well as its administration costs and associated labs must be fully covered without cost sharing, and without forcing people to take an oral option instead. People with no insurance or inadequate insurance may be able to access the drug through ViiV’s patient assistance program, but must have a prescription from a care provider. It’s too soon to know how the roll out of Apretude will go, but advocates should follow closely using an equity lens to ensure that all persons have convenient and equity-based access to all available PrEP options. In addition, a recent court ruling eliminates the requirement that insurers pay for PrEP and PrEP-related services creates a new barrier and should be addressed legislatively.

Activist Joey Wynn:

Studies found Apretude to be superior to Truvada in preventing HIV acquisition. Apretude is an injection, so this is not for everyone. This revolutionary formulation will have a huge impact in dramatically reducing new cases of HIV in the U.S. Barriers removed can include the burden of taking pills and going to the pharmacy for pick up, co-pay costs, and all the other headaches of getting and taking pills. Now we will get to see a majority of folks staying on their PrEP year round.