Who discovered the first drug and how
30 years of developing anti-HIV drugs
There are six different classes of drugs. Each class is different. Around 30 drugs are based on 25 different active ingredients. Most of them contain an active ingredient, but there are also two or three combinations in one tablet.
1981: AIDS is recognized as a disease in its own right on December 1, 1981.
1983: Françoise Barré-Sinoussi and Luc Montagnier discover the HI virus type 1 at the Pasteur Institute in Paris. The US researcher Roberto Gallo from the National Institutes of Health (NIH) also claims the discovery.
1985, February: In the USA, the Japanese virologist Hioraki Mitsuy (NIH) has proven the effectiveness of azidothymidine (AZT) - also known as zidovudine (ZDV) - against the HI virus (HIV). One synthetic cancer drug that has actually failed is AZT, a nucleoside reverse transcriptase inhibitor (NRTI). It inhibits the activity of a key enzyme and thus prevents the virus from replicating.
July: The phase I study for AZT begins with 35 patients at the NIH and the Medical Center of Duke University.
1986: Luc Montagnier discovers HIV type 2 in a West African patient.
December: The British company Burroughs-Wellcome (now GSK) submits the application for approval for AZT to the US Food and Drug Administration (FDA).
1987, March: On March 20, the FDA granted an AZT drug approval for the treatment of HIV - due to the special circumstances there was no prior phase III study or large-scale study. The cost of treatment for the drug is $ 10,000 per patient annually.
1989: A new antiretroviral drug with ddl (didanosine) may be sold in the USA before it is approved.
American studies confirm a preventive effect of AZT. In Europe, the Concorde study with 1700 HIV-infected people is interrupted for ethical reasons. Since some of the test subjects took a placebo, the doctors no longer considered it justifiable to withhold the protection of AZT from them. This decreased the validity of the study.
1990: The FDA also allows the antiretroviral substance ddC to be prescribed prior to approval.
1993, April: The end of monotherapy is looming when the European Concorde study finds no added benefit from AZT. The disease progresses almost equally quickly in those treated with AZT and in those who have not been treated.
June: The inventor of the polio vaccine, the US virologist Jonas E. Salk, presents immunotherapy against AIDS. In the end it has no effect. The difficulty in vaccine development is that the virus cannot be neutralized with antibodies due to the many mutations.
1995: Studies show that combined treatment with two active substances is better than monotherapy. A two-way combination of AZT with ddl or ddC is becoming the standard antiretroviral therapy in the fight against the virus.
The FDA approves saquinavir, the first protease inhibitor. It was approved in Europe in October 1996. Patients have to take very high doses every eight hours throughout the day.
1996: The introduction of highly active antiretroviral therapy (HAART) is considered a breakthrough. She is now relying on a combination therapy consisting of at least three antiretroviral drugs (ARV) from two classes of active substances. This prevents the consequences of an uncontrolled HIV infection. The active ingredients of HAART are primarily reverse, transcriptase, proteinase and entry inhibitors, which are intended to prevent entry into the host cell, as well as fusion inhibitors. Opinions differ about the timing of the therapy. Some experts expect normal life expectancy if therapy is started early.
However, the side effects were still very high at the time, so that others spoke out in favor of taking it later. Adherence to therapy, the so-called compliance, plays an important role.
March: The protease inhibitors indinavir and ritonavir received approval in the USA and Europe. While indinavir was given in high doses, the dose of ritonavir could be reduced by increasing the drug's plasma level. The virus is also directed against the other protease inhibitors through cross-resistance. Ritonavir is now used in low doses as a booster to increase the active ingredient levels of other drugs.
September: Nevirapine is the first representative of the non-nucleoside reverse transcriptase inhibitors (NNRTIs) to be approved in the USA (Europe: 1997). NNRTIs are developing into an important component of combination therapies.
1997, March: The protease inhibitor nelfinavir is launched in the USA (Europe: 1998).
June: The NNRTI delavirdine may be prescribed in the US but is not approved in Europe.
1998, June: The FDA approves the first phase III study of HIV vaccines to be tested in humans.
October: The NNRTI efavirenz can be used in the USA (Europe: 1999).
1999, February: At the retrovirus conference in Chicago, the reputation of protease inhibitors as the most effective class of antiretroviral drugs is scratched. Triple combinations of three NRTIs or two NRTIs and one NNRTI achieve better results in comparative studies than the effects of two NRTIs and one protease inhibitor.
2000, November: FDA approval for a triple combination pill with the active ingredients AZT, 3TC and abacavir. One month later it can also be used in Europe.
2002, February: The nucleotide reverse transcriptase inhibitor (NtRTI) tenofovir is approved for all member states by the EU Medicines Agency (EMEA).
2003, March: The first fusion inhibitor with the active ingredient enfurvirtide receives approval. It prevents the cell membrane from fusing with the virus.
June: The protease inhibitor atazanavir can be used in the USA.
July: The FDA approves the NRTI emtricitabine.
2004, December: The STEP study with a new HIV vaccine concept is launched. It's about stimulating the T-cell response, which would be a breakthrough in the search for effective HIV vaccines. The study was designed to prevent new infections and / or reduce the viral load in those who became newly infected with HIV during the study.
2005: Start of the first clinical studies on integrase inhibitors. In addition to reverse transcriptase and protease, integrase is one of the key HIV enzymes. It builds strands of viral DNA into the host cell's chromosomes.
2006, June: The protease inhibitor darunavir can be used in the United States.
July: The FDA approves a three-way combination of efavirenz, emtricitabine and tenofovir in one drug. The remedy only needs to be taken once a day. The monthly cost of the drug is $ 1150.
2007, August: The first CCR5 inhibitor with the active ingredient maraviroc is approved in the USA and Europe (September). It inhibits viruses that penetrate the body's cells via the CCR5 co-receptor.
October: The integrase inhibitor raltegravir takes the "fast track", the accelerated approval, in the USA, and may also be brought to market in Europe (December). He is the first to introduce a new class of drugs.
Another damper in the search for an HIV vaccine: the STEP study is stopped because those vaccinated become infected more often than those in a control group - despite the formation of antibodies.
2008, December: Françoise Barré-Sinoussi and Luc Montagnier receive the Nobel Prize in Medicine for their discovery of the HI virus.
2009: New hope for vaccine research: American scientists discover broad spectrum antibodies in a person infected with HIV.
October: A large global HIV vaccine study by the US Army and local authorities in Thailand is said to have reduced the risk of infection by 30 percent. But the positive data do not stand up to a second analysis.
2012, July: The FDA approves an AIDS prevention drug. It consists of the nucleoside reverse transcriptase inhibitors (NRTIs) emtrictabine and tenofovir disoproxil and is considered a milestone. The remedy is intended for adults who have a high risk of infection. In this case, experts speak of pre-exposure prophylaxis (PrEP).
2013, April: Another setback in vaccine research: In the USA, the government stops testing the HIV vaccine HVTN 505.
2015, April: A study by Rockefeller University in New York shows for the first time therapeutic success with cloned antibodies in an HIV vaccination. The number of viruses in the blood quickly drops significantly.
A pharmaceutical company applies to the FDA for approval of a combination preparation with the active ingredients emtricitabine and tenofovir alafenamide (TAF).
July: American researchers find out that the active ingredient PEP005, which is used against skin cancer, lures the HI viruses out of the reservoirs.
October: HIV co-discoverer Dr. Roberto Gallo tests human tolerance of an HIV vaccine at the Institute for Human Virology at the University of Maryland.
November: FDA approval for a single tablet with four active ingredients (TAF, Emtricitabine, the integrase inhibitor Elvitegravir and the active agent cobicistat).
Looking to the future of HIV treatment:
Vaccinations against HIV remain the main goal of research. However, this also goes in the direction of functional healing. The virus is supposed to be controlled by the immune system itself, not tablets. Research into gene therapy - such as at the Charité in Berlin with blood stem cells - is already underway.
Until 2019: According to the Association of Research-Based Drug Manufacturers (vfa), five other HIV drugs are being developed for HIV therapy, which, among other things, are to introduce two further principles of action: attachment and maturation inhibition. With each new mode of action, the chances that HI viruses can be permanently blocked from multiplying in patients increase. One of the drugs is also being tested for its suitability for HIV prevention.
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