Second patient goes HIV-free

08 March 2019

HIV-VIRUS-PARTICLE

HIV: artists impression of the virus particle

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An HIV-infected patient has successfully cleared the AIDS virus from his body, UK doctors reported this week...

The dangers of HIV infection, and the resulting destruction of the immune system, are well known. Nevetheless, modern anti-retroviral therapy regimes, which suppress HIV replication to undetectable levels, have led to significant improvements in disease prognosis and extending life expectancy. But the cost of these treatments, side effects, and rise of viral resistance to the therapy, mean that a cure capable of ridding patients of the infection still remains a major medical priority.

This week, in a letter to Nature, Ravindra Gupta and his team University College London (UCL) report a further step towards this goal with the durable elimination of HIV from a patient's bloodstream - for the second time in history.

This was achieved by transplantation of hematopoietic stem cells, the cells capable of regenerating all the cells in the blood, from a donor whose own cells carry a mutation rendering them resistant to HIV.

HIV infects a subset of immune white blood cells called CD4 T-cells. It gains entry to these cell by latching onto receptors on the cell surface. These include the CD4 molecule as well as a so-called chemokine "co-receptor", one of which is dubbed CCR5. But individuals who carry a mutation in the gene that codes for the CCR5 co-receptor are resistant to HIV infection. In Europe, this change is present in about 1% of the population, meaning that these individuals are much harder to infect with HIV.

The patient treated by the UCL team was also battling lymphoma, a cancer of immune cells, which is a common complication of long-term HIV infection. To treat the lymphoma, the doctors first used drugs to destroy both the lymphoma and also the patient's own bone marrow cells.

Next, they administered into a vein bone marrow stem cells collected from the donor who, by chance, also harboured the CCR5 mutation that gives resistance to HIV. The donor's stem cells "took" in the recipient and generated a new bone marrow, which also began to churn out white blood cells, restoring the immune system in the patient.

Critically, because these new donor cells were endowed with the CCR5 mutation, the patient's HIV was unable to infect them. Eighteen months later the patient stopped taking any antiretroviral drugs, and now, 34 months after the transplant, there is no detectable HIV in his bloodstream. His new immune system also appears to be functioning well.

This patient is the second to be apparently "cured" of HIV in this way, and the result is significant because it means the successful treatment of the first patient maanged this way was not just a lucky exception. It also suggests that this is a promising avenue to pursue in our quest for a long-term HIV cure.

Unfortunately, this approach won't work in all HIV-infected patients. The two HIV-free patients described so far had to undergo destruction of their own bone marrow as part of cancer treatment. 

Following their transplants, both patients experienced a mild form of graft-versus-host disease, an immune reaction in which the donor immune cells attack their new host. While this helped to eradicate remaining host HIV-sensitive T cells, it does lead to damage to other tissues and organs, so it is not appropriate as a general therapeutic measure. A more widely prescribed cure would require a safer way to remove HIV-sensitive cells.

Importantly, both patients also carried a strain of HIV whose infection cycle depends on CCR5 as a co-receptor. Other strains of HIV exist that rely on a different co-receptor, called CXCR4, and these viral strains can still infect CCR5-mutant cells, so this approach would not be expected to work in every HIV patient.

Nevertheless, these latest results support targeting CCR5 as a therapeutic approach for HIV infection, possibly involving a gene-editing strategy designed to introduce a mutation into the CCR5 gene of a patient’s own cells, although it's still early days...

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