Scientists reveal AIDS functional cures

Scientists reveal AIDS functional cures

December 03, 2018 Source: Chinese Journal of Science

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American scientists have discovered two HIV-infected people whose immune cells behave differently from other virus-infected people and can still control viral load after several years of infection. In addition, the two patients were infected with a large number of viruses, but blood tests showed no viral load. The researchers believe that although based on only a small number of patients, the results suggest that long-term viral remission is possible for more people.

The results of this study were published online in the Journal of Clinical Investigation and Observation.

Joel N. Blankson, a professor at Johns Hopkins University School of Medicine, said: "One of our patients was infected with HIV almost 20 years ago and terminated after several years of antiretroviral therapy (ART). It has been in a 'viral-free' state for 15 years after stopping ART. Our findings suggest that the patient's immune system can be reset early by ART, and even if the treatment is stopped, the virus can still be controlled." In addition, he added: "Understanding the mechanism by which this happens can help HIV-infected people achieve a 'functional cure'."

HIV infects the immune system's CD4+ T cells and uses these cells for viral replication to produce more viruses. In the early stages of infection, another type of immune cell (CD8+ T cells) recognizes and kills HIV-infected CD4+ T cells. However, under normal circumstances, the speed of virus replication is very fast, and eventually CD8+ T cells will not be able to keep up with the speed of virus replication, and they will also apoptosis.

In this new study, researchers have been focusing on two HIV-infected individuals who do not detect HIV levels in routine testing. One of them, known as the elite virus suppressor, carries a special genetic marker on his immune cells, so that his body can naturally maintain low virus levels without treatment; another patient is a so-called therapeutic acquisition. The virus controller, who received ART for several years, stopped the treatment 15 years ago and did not carry any protective genetic markers.

As part of a patient's regular visit to the clinic for many years, their blood is collected for viral load testing. The researchers isolated CD4+ T cells from their blood samples. Although there is no measurable level of viral load in their blood (an unusual feature of HIV-infected individuals who can control the virus), both patients have large numbers of HIV-infected CD4+ T cells.

Previously, the presence of large viral pools in CD4+ T cells was considered a major obstacle to eradication of HIV because it contains a large number of viruses that can replicate and spread rapidly. However, this does not seem to happen to these patients, and the researchers then conducted further research to determine the cause.

Through the samples collected from patients over the years, the researchers isolated the virus from the virus controller's sample and sequenced the viral genetic material. They found that the virus in the 2010 sample was exactly the same as the other two samples collected in 2017 at intervals of six months. This result is surprising because usually when the HIV virus replicates, the virus constantly mutates, and as a natural evolutionary process, the most adaptable version of the virus will continue to multiply.

Blankson pointed out: "The fact that these viruses are identical shows that the virus is replicated through a process called clonal amplification. That is, the infected resting cells in the virus reservoir divide, resulting in the exact replication of all viral genes. ."

After determining that the viruses were identical, the researchers then examined whether the CD8+ T cells controlled the virus to some extent. The team isolated CD8+ T cells from each patient and mixed them with virus-infected CD4+ T cells from the same patient; they also CD8+ T cells from other non-viral controllers and their own infected CD4+ T cells mixing. The researchers eventually found that the CD8+ T cells of the virus controller could inhibit the virus in the body, while the CD8+ T cells of the non-virus controller could not suppress the virus. This suggests that although virus controllers also have a large number of infected CD4+ T cells, they are still able to maintain viral load below the detection level for a long time, and the behavior of CD8+ T cells is critical.

Dr. Rebecca T. Veenhuis of the school's medical school said: "We believe this is the first time that HIV-specific CD8+ T cell responses have been found in the treatment of acquired virus controllers. The results of this study indicate that despite the existence of a huge virus pool, Functional cures are still possible."

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