First Long-Acting Injectable PrEP Comes of Age

A New Prevention Option
The First Long-Acting Injectable PrEP Comes of Age
by Chael Needle

Apretude, the first and only long-acting injectable pre-exposure prophylaxis for adults and adolescents (weighing at least 35 kg) at risk of acquiring sexually acquired HIV-1, was recently approved by the FDA.

Manufactured by ViiV Healthcare, the global specialist HIV company majority owned by GlaxoSmithKline plc (GSK), with Pfizer Inc. (Pfizer) and Shionogi Limited (Shionogi) as shareholders, Apretude, or cabotegravir extended-release injectable suspension, was approved based on study trials that enrolled men who have sex with men; women; and transgender women who were at increased risk of sexually acquiring HIV (7,700 participants across thirteen countries combined). The two international Phase IIb/III multicenter, randomized, double-blind, active-controlled trials, HPTN 083 and HPTN 084, evaluated the safety and efficacy of cabotegravir long-acting for PrEP. Cabotegravir is an integrase strand transfer inhibitor (INSTI).

The prepared release pointed out that “the blinded, randomized portions of both trials were stopped early by an independent Data Safety Monitoring Board after cabotegravir long-acting for PrEP was shown to be superior to daily oral emtricitabine/tenofovir disoproxil fumarate (TDF/FTC) tablets in preventing the acquisition of HIV in study participants. Clinical trial participants who received cabotegravir long-acting for PrEP experienced a 69% lower incidence of HIV compared to FTC/TDF tablets in HPTN 083 and a 90% lower incidence of HIV compared to FTC/TDF tablets in HPTN 084.”

The list of the most common adverse reactions (all grades) that were noted in at least 1% of clinical trial participants taking cabotegravir long-acting for PrEP includes injection site reactions, diarrhea, headache, pyrexia, fatigue, sleep disorders, nausea, dizziness, flatulence, abdominal pain, vomiting, myalgia, rash, decreased appetite, somnolence, back pain, and upper respiratory tract infection.

The PrEP regimen involves as few as six injections a year, with an initial single 600 mg (3-ml) injection given for two consecutive months, spaced one month apart. After these two injections, the recommended dose frequency becomes a single 600 mg (3-ml) injection given every two months. Tolerability may be assessed with Vocabria (cabotegravir oral tablets), given to the PrEP user for about one month before initiating the first injection.

As with any PrEP option, patients need to test negative for HIV prior to taking the regimen.

In a prepared release, Deborah Waterhouse, CEO, ViiV Healthcare, said: “People who are vulnerable to acquiring HIV, especially those in Black and Latinx communities who are disproportionately impacted in the US, may want options beyond daily oral pills. That’s why ViiV Healthcare is proud that Apretude was studied in one of the most diverse and comprehensive HIV prevention trial programs to date, which also included some of the largest numbers of transgender women and Black men who have sex with men ever enrolled in an HIV prevention trial. With Apretude, people can reduce the risk of acquiring HIV with as few as six injections a year. Today’s approval is the latest example of ViiV Healthcare’s commitment to developing long-acting medicines that offer consumers a different choice.”

A&U recently corresponded with community-based advocate Gabriel Maldonado, MBA, Executive Director and CEO, TruEvolution.

Chael Needle: Even as Apretude shows superior efficacy in preventing HIV compared with a once-daily oral pill, individuals may not want or be able to go to a healthcare site for an injection. What are some possible ways we can dismantle this barrier?
Gabriel Maldonado: The future of healthcare service-delivery and public health will need to include tools such as mobile clinics and offering supportive services like medical transportation utilizing both in-house vehicles run by healthcare facilities and third-party ride share services like Lyft and Uber.

What do you think are some of the other major barriers to uptake that we need to work on going forward?
Education and stigma. Innovations like Apretude are only as effective as the community’s utilization. We need to continue educating our community on their risks and prevention tools for HIV, and destigmatize peoples perceptions around HIV, sexual health, and the needs of populations most impacted. Stigma and lack of education are often the “invisible barriers” that are the most nuanced and challenging, requiring both a community-wide and one-to-one relationship-building with the communities in greatest need of HIV prevention tools.

To what extent do you foresee health insurance coverage as problematic? I know some individuals on PrEP whose insurance switched them to generic PrEP; Descovy for PrEP is widely available. To what extent might Apretude be inaccessible because of the accessibility of these other options?
There is always confusion and bureaucracy when new therapies become available and the often complicated set of processes to have covered by insurance. Benefits counselors at local healthcare facilities will need to be educated and equipped with the most accurate information on how various health plans and third-party payers are covering Apretude. Individuals from marginalized and vulnerable populations will often give up on pursuing new treatment options if the coverage barriers are too burdensome. Developing a streamlined approach and understandable guidelines on coverage, along with benefits counseling and education, will be essential to minimizing the negative impacts on uptake due to barriers with coverage.


Chael Needle is Managing Editor of A&U. Follow him on Twitter @ChaelNeedle.