But couldn’t the virus also become resistant to GS-6207? To find out, the researchers tested the substance in increasing concentrations in their cell cultures over a period of three months. After a few weeks, virus mutants had actually developed that were less sensitive to the drug. The team also found one of these mutations in the virus strains in one of the HIV-positive test subjects.
“This is not surprising,” says Frank Kirchhoff from the Ulm University Hospital. “So far, resistance has developed with every virus protein that you attack,” explains the virologist. With his team, the Institute of Molecular Virology, he also researches HIV. The use of the new active ingredient only makes sense if it is combined with other HIV medications. Mark Snyder, Managing Director of Gilead, agrees: Lenacapavir (as the pharmaceutical company calls its active ingredient) will need a partner.
“If resistances occur in the individual application, this does not mean that this will also be the case in combination therapy,” says Kirchhoff. Ideally, an HIV patient should be treated in such a way that the virus no longer reproduces. “Then the risk of developing resistance is very low,” explains the virologist. Because only if the virus multiplies and thereby copies its genome, new mutations can arise.
He found the team’s study “interesting and very well done”. What is new and special is that the researchers are not attacking an enzyme in a relatively small amount with their molecule, but rather a structural protein of the virus, says Kirchhoff. “There are a few thousand of these per virus particle.” He regards the high effectiveness of the substance as a plus, as well as its long stay in the body. Perhaps you could combine them with other active ingredients that also work for a long time and thus achieve long-term therapy. “It would be a huge advantage if you no longer had to take the medication every day, but only had to inject it every few months,” says the virologist.
The cocktail of medications that HIV-positive people today have to take every day – and for life – can cause severe side effects, such as nausea, vomiting, liver and kidney damage, mood swings and allergies. If the patients forget their medication, their condition can quickly deteriorate – and they can infect other people.
HIV medication for prevention
Because it works for so long, the drug could also be given to people who have not yet contracted HIV but are at high risk for it, the researchers at the pharmaceutical company write. To do this, one would first have to clarify whether the product actually has no – or at least hardly – side effects. The fact that you have to inject it is not ideal. It is also questionable whether the drug would be affordable for people in developing countries. The costs for potential preparations have not yet been determined, says Gilead managing director Snyder. The application is currently being tested in the form of a weekly tablet.
There is already a drug for the prevention of HIV: PrEP, which stands for Pre-Exposure Prophylaxis. The tablets contain two active ingredients that are also used in HAART therapy. In Germany, they cost between 40 and 70 euros per month. If you take the medication daily, you are protected from HIV infection just as well during sex as when you use a condom. The latter not only protects against HIV, but also against other sexually transmitted diseases. Unfortunately, the use of condoms has still not prevailed everywhere.
HIV and AIDS
The human immunodeficiency virus (HIV) affects certain cells in our blood, so-called T helper cells. They play an important role in immune defense.
It belongs to the family of Retroviren. This means that the DNA of the virus, which consists of RNA, is transcribed into DNA, which is permanently integrated into the genetic material of the host cell. There is a great danger in this: the virus can lie dormant in our cells for years without being noticed. Infected people are often symptom-free for a long time. For a while, the body manages to fight off the virus with the help of antibodies. But the number of T helper cells continues to decrease. The AIDS-typical clinical picture only appears in the final stage: those affected are extremely susceptible to other pathogens; cancer is often added.
The immunodeficiency disorder AIDS (acquired immune deficiency syndrome) first appeared in humans in the early 1980s. Since homosexuals were primarily affected, doctors and researchers suspected a connection. But more and more heterosexual patients appeared – and even children. The HI virus was isolated from a patient for the first time in 1983. Molecular biological studies suggest that HIV-related viruses were transmitted to humans several times from apes or apes in the early 20th century. Different strains of HIV have developed from this. Group M viruses of HIV-1, which originate from a chimpanzee, mainly circulate in the population.
The virus is transmitted from person to person Blood and other body fluids, such as sperm, vaginal secretions and the fluid on the intestinal mucosa. Most often this happens through unprotected sexual intercourse. The virus can also be transmitted from a mother to her child, for example at birth. Body contact in everyday social life, on the other hand, does not pose any risk of infection.
The disease is still not curable. The so-called highly active antiretroviral therapy (HAART) however, allows AIDS to not break out and allow patients to live a largely normal life. However, the infected have to take medication for life, which can sometimes have severe side effects.
Vaccination would probably be the safest protection against HIV infection. Although researchers have made numerous attempts to develop a vaccine, despite some progress, all have so far failed. A large-scale study in South Africa was only discontinued in early 2020 because the vaccine candidate was found to be ineffective. “The problem is diverse,” says Kirchhoff. Because the virus integrates its genome into our genome, the vaccine should completely prevent infection. With other viruses, it is enough to control the infection so well that the person does not get sick. The enormous variability of the virus also makes it extremely difficult to develop an effective vaccine.
But even without a vaccine, the spread of the virus can be managed “by effectively treating as many people as possible,” says Kirchhoff. This has already been achieved in many areas. Perhaps the new active ingredient can help. However, there is still a long way to go before approval is granted. First of all, further tests are needed to prove the safety and effectiveness of the drug. Gilead is already recruiting subjects for a so-called phase II / III study. The drug is to be tested on more than 200 people, including 175 with untreated HIV infection and 36 infected people who have already received a variety of HIV medications. Snyder hopes to “get results in the near future.”