A possible cure for HIV

HIV is a Human Immunodeficiency Virus that affects the immune system. It makes people much more vulnerable to infections and diseases. It is found in the bodily fluids of an infected person such as through blood. The virus can be passed from one person to another though blood to blood and sexual contact. 

A recent article on Science Daily discusses HIV and how it can lie dormant in infected cells for years or even decades. Scientists think unlocking the secrets of this viral reservoir may make it possible to cure and not just treat HIV. A team of researchers led by Zanvil A. Cohn and Ralph M. Steinman at Rockefeller University and their collaborators describe new insights on which cells likely do and do not harbor this latent virus. These researchers think the reservoir of latent virus may be hiding out in a type of CD4 T cell: long-lived memory cells that help the immune system remember particular pathogens. 

 I believe that this research is important and will aid in saving many lives in the future. More than 1.2 million people in the United States are living with HIV infection, and almost 1 in 7 are unaware of their infection. Finding a possible cure for HIV will lower these numbers greatly.

Is There a Potential Cure for HIV?

It all started with the “Berlin Patient” in 2007. Timothy Brown was cured of HIV when given the stem cells of another patient who was naturally immune to the disease. When this happened two companies, Sangoma and Calimmune, took the opportunity to attempt to recreate the natural immunity to HIV in a lab. This natural immunity occurs because of a gene mutation on the CCR5 gene which is located on CD4 T-cells. When this gene is disable HIV cannot attack the T-cells.

Sangamo was the first to attempt the recreation in 2009. Lead by Carl June from the University of Pennsylvania, a team of researchers and doctors removed CD4 T-cells from patients with HIV. The study then focused on disabling the CCR5 gene alleles and then returning the modified cells to the patient. It was stated that this did no harm to the patients and the altered genes had a half-life of 48 day, which is expected because “…T-cells are not permanent residents of the body”. In fact, several of the patients in this study even exhibited a decline in their HIV levels.

The next company to attempt to recreate the natural immunity to HIV is Calimmune. In 2013 a team led by David Baltimore and Irvin Chen decided to take a different approach to solve the task at hand. Instead of focusing their work on T-cells, they decided to take advantage of blood stem cells. This approach is different because blood stem cells, unlike T-cells, are permanent residents in the body. During this study patients were “given back both their own T cells, and longer-lived HSCs [blood stem cells], both with the CCR5 gene disabled using hairpin RNAs delivered by a lentivirus.” By doing this they hope that these blood stem cells can continue to produce T-cells with disabled CCR5 gene alleles throughout a patient’s lifetime.

Despite the fact that neither of these studies have conclusive clinical trials yet, Harvard University has decided to be next in the search for a cure for HIV. Their approach will include new CRISPR/Cas technology which has already proven effective in mice. It was stated that Harvard may even apply for clinical trial approval in five years.

Article: http://www.biosciencetechnology.com/articles/2014/11/fighting-hiv-stem-cells-and-cutting-edge-genetics

Related Article: http://www.nejm.org/doi/full/10.1056/NEJMoa1300662

Potential Cure for HIV

According to the World Health Organization (WHO), approximately 0.8% of adults between the ages of 15-49 years old are living with human immunodeficiency virus (HIV) worldwide. Despite the global prevalence of the virus, there has not yet been a functional cure. However, recently an HIV-positive patient with leukemia was cured of the virus. The patient underwent total body irradiation (TBI) and a bone-marrow transplant. The bone-marrow donor had a mutation which prevents the function of the CCR5 gene. The CCR5 gene codes for a protein which allows HIV to enter human cells. The mutation the donor possessed, however, protects cells against HIV infection.

Experts believe three factors may have contributed to the cure in the Berlin patient. The first factor which may have contributed to the patient’s cure is that the removal of blood and immune cells  which occurred after irradiation killed many of the viral reservoir cells. The second contribution may have been that the CCR5 deletion mutation from the donor cells protected those cells and their progeny from HIV infection. The third contribution to the patient’s cure may have been a graft versus host reaction which resulted in the transplanted cells and their progeny attacking and eliminating the remaining HIV-positive cells.

In order to further research this potential cure for HIV, a study was conducted involving six rhesus macaques infected with simian immunodeficiency virus (SIV). The researchers harvested hematopoietic stem cells from three of the six of the macaques prior to infection with SIV and treated the macaques with antiretroviral therapy (ART). They treated the three macaques from which they collected hematopoietic stem cells with high doses of radiation. The radiation killed 94%-99% of the monkeys’ CD4-T cells. The three monkeys then received their own virus-free hematopoietic stem cells. The viral load rebounded rapidly in the three control group monkeys and in two of the monkeys who received the transplant. Due to the failure of the treatment, the researchers suggest that “the use of the CCR5 mutant donor and/or the presence of graft versus host disease played a significant role” in the cure of the Berlin patient.

Overall, this potential treatment for HIV seems to have promise and should definitely be more extensively researched. This treatment involving ART, irradiation, and a hematopoietic stem cell transplant is very complex, and there are many aspects of it which should be thoroughly examined. I found this article extremely interesting because the graft versus host disease in the Berlin patient seemed to have been a vital factor in how the patient was cured of HIV. Due to the complexity of the Berlin patient’s case, the results will be difficult to replicate; however, replication of the Berlin patient’s results has profound implications in the search for a cure for HIV.

Article: http://www.sciencedaily.com/releases/2014/09/140925141220.htm

Related Article: http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004406