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Breakthrough in fighting AIDS?

Breakthrough in fighting AIDS?

In early March 2019, the world was shocked to hear the news of the second successful attempt to cure HIV infection. Since this news is as significant as it is sensational, we asked Dr hab. Monika Bociąga-Jasik from the JU MC Chair in Gastroenterology, Hepatology and Infectious Diseases to explain this phenomenon. Are we witnessing a revolution in our struggle with HIV?


Since 1981, when doctors in the US noted a rise in pneumocystis pneumonia and Kaposi’s sarcoma in previously healthy young men who had sexual contacts with other men (MSM), there have been tremendous advances in our knowledge about HIV infection and its treatment. In 1985, only two years after the discovery was made, first attempts were made to treat HIV using zidovudine (ZDV, a antiretroviral medication).

After a short pilot experiment coupled with a double blind test performed on as few as 282 patients, ZDV was quickly accepted by leading figures in medicine and entered the market two years later. Unfortunately, it quickly became apparent that due to HIV’s rapid development of immunity against ZDV, treatment based on a single antiretroviral medication yields no success. Only after achieving better understanding of HIV replication in the following decade did researchers manage to produce new types of antiretroviral drugs and employ combination therapy (HAART – Highly Active Antiretroviral Therapy), allowing them to control the infection and halt its progress.

The Berlin Patient – the first person to overcome HIV

CCR5 mutation preventing HIV from invading a T-cell. Image: Nature Reviews Immunology

Currently, as long as it is detected early, the infection is treated as a chronic disease, and patients’ lifespan is comparable to that of an average person. Alas, in spite of very effective antiretroviral drugs, doctors have not been able to eradicate HIV from the organism with conventional methods. Moreover, constant production of new HIV particles as well as loss of integrity of mucous membrane in the digestive system and the following exposure to intestinal bacteria lead to increased activity of the immune system. As a result, people with HIV have a higher risk of suffering from cancer, cardiovascular diseases, and other illnesses.

From the time that AIDS was discovered, HIV has infected about 75 million people worldwide. Despite advanced treatment techniques, until recently there has been only one confirmed case of successfully curing the infection – Timothy Ray Brown, ‘the Berlin Patient’. The man, who suffered from acute granulocytic leukaemia, has received an allogeneic bone marrow transplant from a donor carrying the homozygous mutation of the CCR5 co-receptor (CCR5Δ32/Δ32). This particular mutation causes the surface of T-cells to be devoid of CCR5 co-receptors, which HIV (R5-tropic) uses to enter cells.

When discussing Timothy Brown’s case, it is necessary to remember that his cancer was treated with whole body radiation therapy and that he went through the graft-versus-host-disease (GVHD), one of the most grave complications of the haematopoietic system cell transplants, where T-cells recognise the recipient’s organism as hostile and start attacking it. Both of these could be a factor in HIV eradication. In 2007, the patient stopped taking antiretroviral medication after ending his anti-cancer treatment. The doctors were unable to find any traces of HIV replication. Timothy Brown was declared healthy.

The London Patient – the light at the end of the tunnel?

Timothy Brown. Photograph by Zhaolin Hua, Institute of Biophysics, Chinese Academy of Sciences

In early March, Nature informed about a second supposed case of HIV eradication in the UK. It was also announced on the Conference on Retroviruses and Opportunistic Infections (CROI), one of the most important international conferences devoted to antiretroviral therapy, which this year was hosted in Seattle.

‘The London Patient’, as the media dubbed him, was diagnosed with AIDS in 2003. Antiretroviral treatment began nine years later. In 2016, he started developing Hodgkin’s lymphoma – a type of cancer much more often seen in patients infected with HIV. For that reason, just as the Berlin Patient, he received an allogeneic bone marrow transplant with the same co-receptor mutation – in this case, the only one used by HIV to invade C4+ T-cells. Similarly to Timothy Brown, the London Patient suffered from GVHD. Antiretroviral treatment was stopped 16 months after the transplant.

As of now, the patient has been in remission for 18 months. Doctors were unable to find any trace of HIV-RNA in his blood, and what’s more important, there’s also no HIV-DNA built into C4+ T-cells, which suggests that the virus is also absent in ‘reservoirs’, such as the central nervous system, genitals, and lymphatic nodes. It is those reservoirs, in which the virus is stored in its inactive form, that prevent drugs at our disposal from eliminating HIV in the human organism at different stages of replication. The doctors have also noted a decrease in HIV-1 antibodies, like in the case of the Berlin Patient.

It is not yet safe to firmly state that it is the second case of full elimination of HIV, and not just temporary remission. Additionally, the treatment is not a solution that could be used for the majority of the patients that were previously successfully treated with antiretroviral drugs, but did not experience any cancer-related complications. Bone marrow transplant carries too high of a risk of dire side effects, and is extremely expensive to boot.

Nevertheless, it definitely is another breakthrough, providing scientists with clues in their search of methods to completely eradicate HIV from people’s organisms. It’s a ray of hope, because although there have been great advances, AIDS is still a dangerous chronic disease that may result in serious complications, including cancer, and is often accompanied by ostracism and lack of social acceptance.

Sources:

  1. Gupta R.K. et al.: HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation. Nature 2019, March 5 (Epub ahead of print).
  2. Cohen J.: Has a second person with HIV be cured? Science 2019, 363, 1021.
  3. Mitchell B.I. et al.: Impact of Meyeloid Reservoirs in HIV Cure trials. Curr HIV/AIDS Rep. 2019, March 5 (Epub ahead of print)

Original text: www.nauka.uj.edu.pl

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