Accessibility and Innovative Uses

While progress in developing highly effective and safe HIV treatment and prevention (PrEP) medications has been nothing but miraculous over the past two decades, approximately 25% to 30% of persons with HIV (PWH) do not have well-suppressed (or undetectable) HIV and only about 33% of persons who could benefit from PrEP are receiving it.

Suffice it to say, while the many one-pill, once-a-day medication regimens currently available to treat and prevent HIV have worked well for many PWH and those at-risk for HIV, they are not being used by or working for everyone who needs them. Innovation in developing new and better HIV treatments and PrEP has been a consistent characteristic of the HIV drug development industry.

So, what could be as, or more, effective, safe and acceptable as taking one-pill, once-a-day? HIV treatment and PrEP strategies that do not involve daily pills with dosing intervals measured in months instead of days.

Over the past three to four years, three new long-acting injectable medications have been FDA-approved in the U.S and a fourth is slated to be approved later this year or in early 2025. These medications currently offer PWH the option to receive highly effective, safe and well-tolerated treatment and PrEP for HIV by receiving an injection once every two or six months.

Two of these new drugs — Cabenuva for treatment and Apretude for PrEP — contain cabotegravir, a highly potent anti-HIV drug known as an integrase inhibitor. Cabenuva also contains a second medication called rilpivirine (an NNRTI). Both of these drugs are formulated as a liquid which can be easily injected into a muscle, usually in the buttocks, and provide treatment or protective levels of these drugs for at least two months.

Since these two drugs became available in the U.S. in 2021, their use has steadily increased primarily due to not only their effectiveness and lack of serious side effects, but primarily because of the overwhelming preference among persons receiving them. Not only is the “work” of obtaining, storing, managing, administering and refilling medication prescriptions taken on by the medical provider, but also the internal and external stigma of being HIV positive, which is re-enforced daily by taking a pill, having the pills discovered by others not aware of ones HIV or at-risk status, or being labelled as an “infected” or “promiscuous” person, is alleviated.

This second benefit of relieving/avoiding HIV stigma has been a driving incentive for many persons to choose Cabenuva and Apretude. While high prices for new medications like these is always an issue for obtaining them, both MediCal (California’s Medicaid) and Medicare as well as almost all private insurance payors cover the costs of these drugs.

A third medication called lenacapavir, the first of a new class of HIV medications called capsid inhibitors, became available in the U.S. as a new HIV treatment in late 2023.

Lenacapavir’s primary advantage is that following two oral doses on the first two days of treatment along with two injections just beneath the skin (subcutaneous injection, similar to how insulin is injected), this new medication is continued as two injections given once-every-six-months. So far, the FDA has approved lenacapavir only for PWH with highly drug-resistant HIV and must be given with at least two other HIV medications, usually pills dosed once or twice daily. The full promise of lenacapavir for HIV treatment will be realized when it can be used with other long-acting HIV medications which can also be dosed less frequently than daily and hopefully once-every-six-months.

Lenacapavir’s most exciting new use is yet to be realized. Over the past 4 months, the results of two large, international, phase 3 clinical trials called the PURPOSE-1 and PURPOSE-2 studies were announced. Both studies evaluated the use of lenacapavir (dosed as above) versus daily pills for PrEP among young (18-24 years of age), cis-gender women in sub-Saharan Africa (PURPOSE-1) and men-who-have-sex-with men (MSM), transgender women (TGW), transgender men (TGM) and non-binary persons (PURPOSE-2).

While the details of the PURPOSE-1 study have been publicly presented and published in a high impact, peer-reviewed medical journal, the results from PURPOSE-2 have been publicly presented but not yet published. In both studies, persons receiving lenacapavir had so many less new HIV infections than those receiving the two currently FDA-approved oral medications (Truvada and Descovy), that the blinded phase of both studies were prematurely stopped, lenacapavir was declared to be superior to the oral medications and all persons enrolled in the study were offered continued PrEP with lenacapavir. Of note, this was the same result as the two clinical trials evaluating Apretude (cabotegravir; see above) compared to daily oral PrEP (Truvada).

One of the most exciting and new, but still under study, uses of these long-acting, injectable medications is treatment of PWH and PrEP for those at-risk for HIV experiencing homelessness in Los Angeles County. An overwhelming daily challenge these persons encounter living on the street is maintaining security of their possessions, especially any pills in or out of a prescription bottle. Too often, these person’s possessions are stolen, lost in a raid of their tents, or sold on the street for survival.

Expecting people experiencing homelessness to maintain consistent clinic appointment attendance is ignoring the tremendous daily challenges these people face.  I personally experienced this while making Street Medicine Rounds with colleagues in the USC Family Medicine’s Street Medicine Program. While repeatedly hearing from PWH and those at-risk for HIV that the bottle of pills given to them was stolen, lost, or bartered, it became clear to me that this situation is a perfect application of long-acting, injectable HIV treatment and PrEP.

Under the direction of the Keck School of Medicine of USC Department of Family Medicine’s Street Medicine Program, the pioneering use of long-acting Cabenuva and Apretude has slowly begun in a small number of people experiencing homelessness. One of the most innovative and solution-oriented aspects of long-acting, injectable HIV medications is its portability. It can easily and efficiently be taken to the persons needing it, administered and repeated on a regular basis. Many people experiencing homelessness in LA County have a cell phone and can be contacted directly. Their location does not frequently change unless a traumatic event occurs (raid, personal violence or relocation).

More will be revealed as this program grows and expands the use of long-acting injectable HIV treatment and PrEP for people experiencing homelessness.

Equity in access to these major lifesaving and HIV prevention strategies is critical, especially since the clinical trials to demonstrate their safety and efficacy are primarily conducted in low- and middle-income countries (sub-Saharan Africa, South America and Thailand).  For this reason, the manufacturers of Cabenuva and Apretude (ViiV Healthcare) and lenacapavir (Gilead Sciences) have committed to making their patented and proprietary drug manufacturing intellectual property available to multiple generic pharmaceutical manufacturers primarily outside the U.S.

ViiV is working to transfer its manufacturing technology via the Global Patent Pool and Gilead is signing contracts with generic manufacturers in India, Pakistan, Egypt and the U.S.  While Gilead’s contracting will allow equitably priced generic products to be made and sold in many low-income countries primarily in sub-Sahara Africa, several middle-income countries such as Brazil, Colombia, Argentina and South Africa will not be allowed to purchase lenacapavir from the generic manufacturers.

This raises concerns, as over 20% of new HIV infections occur in these countries. Overall, the commitment by both pharmaceutical companies underscores their dedication to making sure that their innovative products not only reach PWH and those at-risk in high-income countries, but also for many who could benefit from them around the world.