Some HIV drugs in development

Effective combination HIV treatment was introduced in the mid-1990s in North America. For the first time in the history of the HIV pandemic, treatment was able to reduce the risk of serious AIDS-related complications. In that era, treatment was complex, often involving a fistful of pills at least two and sometimes three times daily, in many cases with food and water requirements. What’s more, treatment back then had many side effects.

Since that time, pharmaceutical companies have developed more effective and simpler regimens. In many cases an entire regimen (two or three potent drugs) can be packed into one pill taken once daily.

Another advance has been the creation of long-acting medicines. In the year 2020, regulatory authorities in Canada approved the first long-acting HIV treatment. This was a combination of two drugs—cabotegravir + rilpivirine (sold as Cabenuva). The combination is injected deep into the buttocks, where it is slowly released into the bloodstream. Clinical trials have found that after monthly injections for two consecutive months, Cabenuva only needs to be injected every two months. Several other long-acting therapies are in development.

Modern HIV treatment (ART) has been so transformative that researchers expect that many ART users will have near-normal life expectancy. However, as people with HIV age, they may need to change their regimens for a number of reasons—for example, if they develop drug-resistant virus or are dealing with side effects or want to simplify their regimen. As a result, the pharmaceutical industry is developing new drugs. In this issue of TreatmentUpdate, we summarize HIV drugs that are coming to clinics in the future.

Lenacapavir

Another anti-HIV drug called lenacapavir has recently been approved in Canada. Lenacapavir works in a way that is different from other HIV drugs—by interfering with an HIV protein called the capsid. The initial approval of lenacapavir will be for people with limited treatment options due to drug-resistant HIV (this population is sometimes referred to as “heavily treatment-experienced patients” by researchers). Lenacapavir is meant to first be taken as a pill three times over the course of eight days. About a week after the third (and final) oral dose, nurses administer two subcutaneous (just under the skin) injections of lenacapavir in the belly. After these initial injections, additional injections are administered every 26 weeks (roughly every six months). For now, lenacapavir will need to be taken with other HIV drugs (as daily pills). However, it is possible in several years that there will be other drugs equally as long acting as lenacapavir. This could remove the need for daily pill-taking in the long term. Lenacapavir is also under development for the prevention of HIV—pre-exposure prophylaxis (PrEP). We have more information on lenacapavir later in this issue of TreatmentUpdate.

Islatravir

Another emerging HIV drug is islatravir, which is being tested as part of dual combination therapy with another drug called doravirine (Pifeltro and in Delstrigo). Islatravir has long-acting potential and will hopefully be tested in clinical trials with lenacapavir.

Maturation inhibitor

The experimental drug GSK 3640254 is set to enter clinical trials sometime in 2023. This HIV drug belongs to an emerging class of medicines called maturation inhibitors. It will be tested in combination with other anti-HIV drugs.

Lenacapavir is the first of the three drugs previously mentioned to be approved in Canada. If all goes well, the two other drugs (Islatravir and GSK 3640254) will hopefully be approved in several years.

—Sean R. Hosein