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Tenofovir or how to go antiviral
Research

Tenofovir or how to go antiviral

KU Leuven has a longstanding tradition in contributing to the development of innovative and effective drugs.

5 minutes
02 December 2019

KU Leuven has a longstanding tradition in contributing to the development of innovative and effective drugs. Owing to the work of a few trailblazing scientists, a new generation of powerful anti-HIV/AIDS treatments arrived onto the market. One example is tenofovir, the most commonly used anti-HIV drug in the world. Stemming from a successful collaboration between researchers at KU Leuven, Prague's Academy of Sciences and Gilead Sciences, the drug manages to ‘go anti-viral’, and enables those infected to lead full and qualitative lives.

KU Leuven-Discovered Drug Continues to Prove Triumphant in the War against HIV

Since the first cases of HIV were reported more than 35 years ago, 78 million people have become infected with HIV. To date, a staggering 32 million people have lost their lives because of AIDS-related illnesses. For many years, the medical world has made continuous efforts to close the book on the AIDS epidemic. One thing, however, remains clear: to put a stop to the deadly disease, we need more effective ways to treat HIV. This virus viciously attacks our immune system. If left untreated, HIV will weaken a person’s natural defence against illness to the point the body can no longer defend itself against life-threatening infections and diseases.

Tenofovir microscoop

From chimps to humans

Scientists believe that HIV originated in non-human primates in Central and Western Africa. As far back as the 1930s, the virus was first transmitted from chimpanzees to humans, through the transfer of blood while hunting. Over the decades, the virus spread through Africa, and to other continents. It was not until the early 1980s, when doctors were alarmed by an increasing number of rare types of cancer, pneumonia, and other illnesses, that the rest of the world became aware of HIV and AIDS. Initial reports claimed the illness targeted homosexual men, but as infections spread swiftly, researchers soon realised the disease was not reserved exclusively for the gay community.

Three stages

People can get infected with HIV when coming in direct contact with certain body fluids from a person with HIV, such as blood and semen. For transmission to actually occur, the HIV in these fluids must get into the bloodstream of an HIV-negative person, via open cuts or by direct injection. Once the body is infected, the virus operates in three distinct stages. In the first stage, the virus converts its own RNA into DNA in the blood cell, a process that requires an enzyme called ‘reverse transcriptase’. In the second stage, the viral DNA integrates in the human DNA with the help of the so-called ‘integrase enzyme’. In the final stage, new copies of the viral proteins are carved off via the ‘protease enzyme’, which encourages the viral proteins to leave the cell and to reproduce elsewhere.

Tenofovir flesje

Before anti-AIDS drugs, the HIV virus could spread like wildfire. Fortunately, since the start of the epidemic, scientists have been moving closer to finding a successful treatment. One of the most notorious endeavours in the war against AIDS was the development of tenofovir. Tenofovir was discovered in 1993 by Professor Erik De Clercq and his team from KU Leuven’s Rega Institute for Medical Research, in collaboration with Professor Antonín Holý from the Institute for Organic Chemistry and Biochemistry (IOCB) at the Czech Academy of Sciences, and Dr. John Martin from the American biopharmaceutical company Gilead Sciences. Together, the driven threesome, consisting of a physician (De Clercq), a chemist (Holý), and a pharmaceutical company executive (Martin) managed to turn their joint findings into a highly successful drug.

Tenofovir onderzoeker microscoop

Crucial T-cells

So, how does tenofovir work? The drug blocks an enzyme the virus needs to embed itself in a healthy cell and to programme itself to replicate. At the same time, it increases the number of crucial T-cells, or the virus-fighting immune system cells HIV targets. Whereas tenofovir can successfully reduce the amount of HIV-infected cells in the blood on its own, it is most effective when combined with other compounds. When patients are treated with tenofovir, the HIV-level in the blood decreases, meaning the infection is no longer deadly, and those infected are able to lead full and qualitative lives. Moreover, clinical trials have demonstrated that tenofovir is also a safe way of treating patients with chronic hepatitis B.

As it stands, tenofovir is the most commonly used anti-HIV drug in the world. The drug was licensed to Gilead Sciences, and the biopharmaceutical company continued to develop it. In exchange for royalties paid to KU Leuven and IOCB, Gilead now produces and distributes the drug under the trade name Viread®, but tenofovir is also an essential component of the combination drugs Atripla®, Complera®, Stribild® and Truvada®.

The latter, Truvada®, is in fact a combination of tenofovir disoproxil fumarate (or ‘TDF’; discovered in 1997) with emtricitabine. In 2004, Truvada® was initially approved by the US Food and Drug Administration (FDA) for the treatment of AIDS. On July 16th, 2012 Truvada® became the first drug approved for the prevention (or ‘prophylaxis’) of HIV infection in uninfected individuals who are at high risk. Incidentally, this was the same day Antonín Holý died. Today, Truvada® remains the only medicine approved by the FDA for the prevention of HIV infection, now commonly referred to as ‘PrEP’, or ‘Pre-Exposure Prophylaxis’.

Tenofovir detail flesje

The FDA has not been resting on its laurels. Soon, Descovy® is expected to be approved by the FDA for the prevention of HIV infection. This drug is the combination of tenofovir alafenamide (TAF, Vemlidy®) with emtricitabine. In the meantime, the FDA has also approved the use of TAF in combination with emtricitabine (Descovy®) and other anti-HIV drugs (Genvoya®, Odefsey®, Biktarvy®, Symtuza®) for the treatment of AIDS.

In its various guises, tenofovir is responsible for billion dollar sales figures. But what about those who cannot afford these treatments? An estimated 10 million third-world patients are currently receiving tenofovir-based HIV-treatment. In 2010, this concern for patients in less well-off areas of the world led the scientists to sign an agreement in favour of HIV patients in 112 developing countries, stating that both KU Leuven and the IOCB of Prague would waive all royalties.

Ending the AIDS epidemic. A bold mission, but we are edging ever closer towards a final solution. According to officials of the Joint United Nations Program on HIV/AIDS, the tools are, in fact, there. With a focus on testing, treatment and prevention, they hope to put a stop to AIDS by 2030. Last year, a mind-boggling 37.9 million people were living with HIV. However, thanks to the development of tenofovir by KU Leuven scientists, they can get another shot at continuing their lives in the best possible circumstances.