Science Magazine just declared as the most important advance of 2024 to the drug lenacapavir. It is one of more than 30 antiretroviral drugs currently available to combat human immunodeficiency virus (HIV) infection, but it has one quality that distinguishes it from the rest: its impressive ability to prevent disease.
Sonia de Castro de la Osa
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Senior Scientist of the CSIC, Institute of Medical Chemistry (IQM-CSIC), Higher Council for Scientific Research (CSIC)
Recent studies have shown that one injection of lenacapavir is able to reduce HIV infections to zero in women for six months. The percentage of effectiveness It is practically the same (99.9%) in gender diverse people who have sexual relations with men. These results significantly improve those of other pre-exposure prophylactic treatments (PrEP) employees today and opens a new path towards hope.
Target: the capsid
Approved in 2022, lenacapavir is considered a “first class” drug, which means that it acts through a different mechanism than the rest of the approved medications. More specifically, it acts as a viral capsid inhibitor. Let’s see what this means.
HIV has an external envelope that protects its interior, where the essential elements are found so that the virus can infect and replicate within human cells. Among them is the capsida cone-shaped structure made up primarily of proteins, such as p24. The capsid not only protects the virus’s genetic material (its RNA), but also envelops the viral enzymes necessary to replicate, such as reverse transcriptase, integrase, and protease.
Furthermore, the capsid plays a crucial role in transporting the viral content to the nucleus of the infected cell, a decisive step so that the pathogen’s RNA can integrate into the cellular DNA and the virus begins to multiply. In short, it not only protects the “heart” of HIV, but also coordinates several key stages of the viral infection cycle.
How does lenacapavir work?
Lenacapavir binds to the capsid, causing its destabilization and interfering in two key stages of the virus’s replicative cycle: the transport of viral genetic material (RNA) into the cell host and the assembly and maturation of new viruses before they exit the infected cell.
By blocking the transport of viral RNA, the drug prevents HIV from replicating in host cells. Even if the virus manages to evade this action, lenacapavir continues to act in a way that prevents the formation of mature virions, which blocks viral spread to other cells.
Because it acts at two different stages of the viral cycle, it is a very effective drug, even against strains of HIV resistant to other treatments.
An additional advantage over other antiretrovirals is its method of administration. Thus, while most of the approved HIV medications They require a daily dose to be effective, lenacapavir only needs a subcutaneous injection every 6 months. This property makes it the most effective long-acting antiretroviral drug available.
And what impact does this have on treatment? Semi-annual dosing significantly reduces the risk of forgetting, simplifies disease management and ensures constant drug levels, improving adherence, a critical factor to keep the virus under control and prevent resistance.
This does not mean that lenacapavir is used as monotherapy (alone) in the treatment of HIV: like the rest of the medications available on the market, this drug is used as part of a combination regimen. –also known as antiretroviral “cocktail”– to ensure effective control of the virus.
Very promising trials
Currently, lenacapavir is indicated for patients with HIV who have significant resistance to other antiretroviral drugs and, therefore, their treatment options are limited. So why has Science magazine now declared it the scientific breakthrough of the year? Well, in addition to recognizing the advances in knowledge about the structure and function of the capsid, this praise values, as we noted at the beginning, the use of lenacapavir in pre-exposure prophylaxis (PrEP).
PrEP is a preventive treatment that consists of administering antiretroviral medications to healthy people highly exposed to HIV in order to reduce the risk of infection. It is primarily aimed at individuals with HIV-positive partners, sex workers or those who practice high-risk sex without the use of condoms.
At the end of June of this year, the company Gilead Sciences announced the results of the clinical trial PURPOSE 1which studied the use of the drug to prevent HIV infection in adult women and girls. In mid-November, the conclusions of the PURPOSE 2which included cisgender men, transgender women, transgender men, and gender non-binary people. Their results showed that treatment with lenacapavir reduced the risk of contracting HIV by an impressive 99.9%. Of the 2,180 people who participated and received the treatment, only two became infected with the virus.
These data have led the World Health Organization (WHO) to choose lenacapavir as “a significant advance” in HIV prevention. Although its preventive use is not yet approved, it is expected to become effective at the end of 2025.
Although these advances represent an encouraging step, it is essential to continue long-term research to confirm its effectiveness and safety in various contexts. HIV remains a complex challenge, and any step forward must be approached with caution, but also with the optimism that science continues to approach new forms of control and prevention.
This article was originally published in The Conversation. Read the original.
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