A significant breakthrough in treating the Human Immunodeficiency Virus (HIV) came recently with the US Federal Drug Administration (FDA) approving lenacapavir, a new prototype medication. It uses a unique mechanism of twice-yearly injections to treat individuals with multidrug-resistant HIV.
The development of lenacapavir by Gilead Sciences has been described by the journal Science as the 2024 Breakthrough of the Year.
It noted that it was “a pivotal step toward diminishing HIV/AIDS as a global health crisis.”
The introduction of lenacapavir is potentially a major step forward in the treatment of HIV/AIDS globally.
It could help achieve UN Sustainable Development Goal 3 which sets the target of eliminating HIV/AIDS as a public health threat and moving towards a sustainable HIV response beyond 2030.
The breakthrough comes at a time when HIV/AIDS remains a formidable challenge in global public health since it was discovered in the early 1980s.
Initially identified in the United States, HIV/AIDS has since claimed more than 42 million lives worldwide and infected more than 88 million people. There were 39.9 million people living with AIDs globally at the end of 2023.
While advancements in antiretroviral therapy (ART, a combination of HIV medicines that treats people infected with the virus) have transformed the management of HIV, it continues to pose significant challenges, particularly for individuals with multidrug-resistant strains of the virus.
HIV originated from zoonotic transmission, likely jumping from non-human primates to humans in Central and West Africa in the early 20th century.
However, it was not until 1983 that French researchers identified the virus responsible for what later became known as AIDS (acquired immunodeficiency syndrome).
This marked the start of a global fight against a virus that devastates the immune system, leaving individuals vulnerable to opportunistic infections and certain cancers.
Antiretroviral therapy, first introduced with the FDA’s approval of AZT in 1987, was a turning point in HIV treatment. Over 50 antiretroviral drugs are now FDA-approved, offering a range of options to manage the virus effectively.
Despite these advances, HIV remains incurable, and many patients face challenges such as drug resistance, requiring new therapeutic innovations.
To understand the impact of HIV, it helps to compare it with the recent COVID-19 pandemic.
COVID-19, largely preventable through vaccines and treatments, differs from AIDS, which remains incurable and can only be managed with antiretroviral therapies.
COVID-19 spread rapidly, causing over seven million deaths worldwide in a short time. Respiratory viruses like SARS-CoV-2 that caused COVID-19 are well-studied, and the targets of vaccine development well characterised.
In contrast, HIV's high mutation rate, integration into human DNA, and long latency period have made vaccine development extremely challenging.
Unlike COVID-19, which mainly causes acute illness, HIV gradually weakens the immune system, leading to chronic vulnerability to infections like tuberculosis, resulting in far higher mortality rates.
Efforts to combat HIV are further complicated by stigma and discrimination, particularly among marginalised communities.
It has been estimated that sub-Saharan Africa, which accounts for 15 per cent of the global population, has two-thirds of the people living with HIV. About 4,000 teen girls and young women are newly infected with HIV every week (2022 figures).
In this context, the FDA’s approval of lenacapavir, a first-in-class drug designed for individuals with multidrug-resistant HIV, is indeed a breakthrough.
Lenacapavir’s efficacy was demonstrated through extensive clinical trials conducted globally, including in many countries in Latin America, South Africa, Thailand and the United States.
The details of the clinical trials study (called PUPOSE 2) conducted by Gilead state, “Lenacapavir was highly effective at reducing HIV infections among trial participants: 99.9% of participants did not acquire HIV in the lenacapavir group, with two incident cases among 2,179 participants (0.10/100 person-years, 95% CI, 0.01 to 0.37).”
This, the study claimed, was despite reported high levels of sexual behavior, chemsex and sexually transmitted infections observed among PURPOSE 2 participants.
The trials highlighted its potential to significantly reduce viral loads, particularly in patients who had exhausted other treatment options.
Lenacapavir has shown high efficacy in managing multidrug-resistant cases, offering hope to patients with limited alternatives.
The procedure for administering lenacapavir involves an initial oral loading dose, followed by subcutaneous injections every six months. Lenacapavir works by targeting the HIV capsid, a protein shell that protects the virus’s genetic material.
The drug is not a standalone therapy and must be used in combination with other antiretroviral medications to ensure comprehensive viral suppression.
Because of its innovative mechanism and extended dosing schedule it has been described as a pathbreaking advancement in HIV care and is being heralded as an early vaccine-like innovation in HIV treatment, providing extended viral suppression that minimises daily treatment burdens.
This simplified regimen improves adherence and reduces the risk of treatment failure due to missed doses.
However, a major challenge in the widespread use of lenacapavir particularly in low- and middle-income countries which have high loads of HIV infections is mainly due to its current cost.
Early pricing has indicated significant disparities, which have led to calls for subsidies and international collaboration to make the drug accessible to those who need it most.
Already, the Global Fund to Fight AIDS has joined hands with several other foundations for a coordinated effort to provide affordable and equitable access to the twice-yearly injectable drug.
This would be subject to “regulatory approval from the U.S. Food and Drug Administration, relevant national pharmaceutical regulators, and a recommendation from the World Health Organization (WHO).”
However, the FDA has now approved the drug. Lenacapavir has also been approved in several countries to treat adults who have multiple drug-resistant HIV, to be used along with other antiretroviral drugs.
There are indications that the drug can also prevent new HIV infections. In October this year, Gilead announced that it has “signed non-exclusive, royalty-free voluntary licensing with six pharmaceutical companies to manufacture and supply high-quality, low-cost versions of lenacapavir for HIV prevention for 120 primarily low- and lower-middle-income countries.”
While the development of lenacapavir is a major innovative step forward in the fight against HIV, it also underscores the importance and need for continued research for more efficacious therapies against HIV including anti-HIV vaccine innovation, and equitable healthcare policies.
The fight against HIV continues, but lenacapavir offers promise for improved management of the infection.
(The author is Chancellor of GITAM University, Arturo Falaschi Emeritus Scientist, International Center for Genetic Engineering and Biotechnology, New Delhi and Distinguished Visiting Professor, Institution of Excellence Delhi University. This article was originally published under Creative Commons by 360info)
