Personalized Medicine: A Cure for HIV

Personalized Medicine – finding the right treatment for the right patient at the right time – is quickly becoming a buzzword both in the medical field but also to the public. But is it just hype? No!  I discussed a number of examples of how personalized medicine is currently be used in breast cancer in a previous post. In this and future posts, I’ll talk about a few fascinating emerging examples of the promise of personalized medicine.  These are NOT currently being used for patient treatment as part of standard of care, but could be someday.


HIV lentivirus

The Human Immunodeficiency Virus (HIV), the cause of AIDS, is a virus that attacks the immune system.  This attack prevents immune cells from fighting other infections.  The result of this is that the patient is more likely to acquire other infections and cancers that ultimately kill them.  When first discovered in the early 1980s, HIV infection was a death sentence. Untreated, survival is 9 to 11 years.  In the past 30 years, antiviral treatments have been developed that, when taken as prescribed, essentially make HIV infection a chronic disease, extending life to 25-50 years. But there is no cure for HIV, and as of 2012, over 35.3 million people were infected with the virus.

The lack of a vaccine to prevent the disease or of a cure to treat those infected isn’t because no one is trying. Since the virus was identified as the cause of the disease, scientists have been working to find a prevention or cure (along with developing all of the antiretroviral drugs that delay/treat the disease). I’m not going to discuss all of this interesting research (though it is worthy of discussion), instead I’m going to talk about one patient, Timothy Ray Brown, who was cured of HIV/AIDS through a stroke of genetic understanding and luck!

Brown was HIV positive and had been on antiretroviral therapy for over 10 years when he was diagnosed with leukemia in 2007. His leukemia – Acute Myeloid Leukemia (AML) – is caused by too many white blood cells in the bone marrow, which interferes with the creation of red blood cells, platelets and normal white blood cells. Chemotherapy and radiation are used to treat AML by wiping out all of the cells in the bone marrow – both the cancer cells and the normal cells. Brown’s doctors then replaced the cells in the bone marrow with non-cancerous bone marrow cells of a donor.  This is called a stem cell transplant, and it is commonly used to treat leukemia – often resulting in long term remission or a cure of the disease.

But the really cool part of this story isn’t the treatment itself.  Rather it’s that that Brown’s doctor selected bone marrow from a donor that had a mutation in the gene CCR5. So what? The CCR5 protein is found on the outside of the cells that the HIV virus infects. CCR5 is REQUIRED for the virus to get inside the cell, replicate, and kill the cell. Without CCR5, HIV is harmless. There is a deletion mutation in CCR5 called delta32 that prevents HIV from binding to the cell and infecting it.  Blocking HIV from getting into the cell prevents HIV infection.  In fact, it’s been found that some people are naturally resistant to HIV infection because they have this deletion. Two copies of the gene are found in 1% of the Caucasian population, and it’s thought that this mutation was selected for because it also prevents smallpox infection.
HIV_ccr5So Brown’s doctors repopulated his bone marrow with cells that had the CCR5-delta32 mutation.  This didn’t just cure his leukemia but it also prevented the HIV from infecting his new blood cells, curing his HIV. He is still cured from HIV today!

What does this mean for others who are infected with HIV? Is a stem cell transplant going to work for everyone?  Unfortunately, no. This mutation is very rare, so finding donors with this mutation isn’t feasible.  Plus, this is a very expensive therapy that comes with risks such as graft-versus-host disease from the mismatch between the person receiving the transplant and the transplanted cells themselves. However, there are possible options to overcoming these challenges, including “gene editing.” In this method, T cells from HIV-positive patients would be removed from the body and then gene editing would be used to to make the CCR5-delta32 mutation in these cells.  These cells could then be re-introduced into the patient.  With the mutation, HIV won’t be able to infect these T cells, which would hopefully cure the disease, while avoiding some of the major graft-versus-host side effects. A small clinical trial tested this idea in 2014 (full article can be found in the New England Journal of Medicine), and HIV couldn’t be detected in one out of four patients who could be evaluated. Although this is a preliminary study using an older gene-editing technique, it shows promise for “personalized gene therapy” to potentially cure HIV.

Are vaccinations needed after a stem cell transplant?

Vaccines are a hot topic. Vaccines bring up lots of discussion, lots of false information, and a vitriolic passion rarely seen in matters of science and pseudoscience. My first post on this topic was about what vaccines are and and what they do. My second post  addressed some of the false information and controversy (with an added bonus of bringing in my lovely sister’s fabulous point of view as a mom of two!) This post will address a question I was asked about whether or not vaccinations are needed after a stem cell transplant.

A friend of mine asked me a question about her friend with non-Hodgkins who was getting a stem cell transplant. He was wondering if he has to get all new immunizations.  Since we have been talking about what immunizations (or vaccines) are and what they do, I thought this would be the perfect place to answer this question.  Before I start, please keep in mind that I’m a doctor, but not that kind of doctor.  This is NOT a medical opinion.  Nothing that I say here should be considered medical advice or used in lieu of talking directly to a doctor.

I won’t give medical advice, but I will explain what is known biologically about why immunizations would be needed after a stem cell transplant.  I won’t go into a lot of detail (in part because I’m not an expert immunologist) but also because there are some interesting resources I can refer you to:


The bone marrow is one of the main organs that makes immune cells required to mount an immune response after infection. Thanks to for the image

Remember the description about how vaccines work.  They induce a “memory” in the immune system that recognizes the infectious agent if it is encountered and kills it before it can kill you. The cells that are responsible for the immune response and creating this “memory” are made in the bone marrow and circulate in the blood (it’s a convenient system because your circulating blood gets access to most of your body so it can find and attack infectious agents quickly).

Non-Hodgkin’s lymphoma is a blood cancer where white blood cells (also made in the bone marrow) divide out of control.  Chemotherapy, one of the main treatments for this kind of cancer, kills the cancer cells circulating in the blood but also kills cells in the bone marrow, including the stem cells responsible for making new blood and immune cells.  With high enough doses of chemotherapy, all of the stem cells in the bone marrow are killed along with the cancer cells. The stem cell transplant replaces the stem cells in the bone marrow which make new blood cells – replacing cancerous cells with healthy blood cells.  Researchers have found that the memory from immunizations often decreases after a stem cell transplant. Part of this is because the cells that have the memory may be killed as part of the chemotherapy and the new immune cells haven’t encountered the vaccine before so they won’t have the memory. Part of it may be because during treatment the patient is on immuno-suppressives.  Part of the reasons also are still being studied or aren’t very clear.

However, either way, it is suggested that immunizations are needed after the transplant – though not necessarily right after transplant.  Again, to reiterate, a doctor will have this information and will be able to provide medical advice.  I’m just giving some background as to biologically why immunizations may be needed after a stem cell transplant.

What are vaccines and how do they work?

Vaccines are a hot topic. Vaccines bring up lots of discussion, lots of false information, and a vitriolic passion rarely seen in matters of science and pseudoscience. I’m going to start my discussion about vaccines by explaining what they are and what they do. My second post will address some of the false information and controversy (with an added bonus of bringing in my lovely sister’s fabulous point of view as a mom of two!) My final post will answer a question I was asked about whether or not vaccinations are needed after a stem cell transplant.

Let’s talk about what immunizations do and how they do it.  Vaccines (aka immunizations) use biological agents to induce an immune response that protects you from that disease. The immunization itself could contain a weakened version of the disease-causing agent (like an inactivated poliovirus to vaccinate against polio), a non-human version of the disease (such as the cowpox virus to vaccinate against smallpox) or a small part of the disease-causing agent (for example, the toxin or a protein on the surface of the disease-causing agent).  The vaccine is injected into the body, but it isn’t strong enough or functional so it doesn’t cause the disease, but the body attacks the vaccine’s biological agent using immune cells and develops a “memory” of this infection.  This memory is made up of both antibodies and immune cells.  Antibodies are shaped like the letter Y and the top part of the Y functions like a puzzle piece that fits together with a complementary piece on the infectious agent (called an antigen).  When the anitbody encounters a matching puzzle piece it will bind to the infectious agent and kill it quickly before it can cause disease. Therefore, the effectiveness of a vaccines depends on how good the vaccine is at making a puzzle piece fits the antigen puzzle piece on the infectious agent.
antibodySo let’s have an example.  The flu vaccine contains small proteins from several flu strains that, when injected, stimulate the immune system to create antibodies against those flu strains.  When a person encounters the flu,for example because their neighbor has the flu and sneezed on them, the antibodies and immune memory that were created by the vaccination will attack and neutralize the flu virus before it can infect the cells and make you sick.  If the flu vaccine didn’t contain proteins that create puzzle piece antigens that bind to the most common flu strain in a particular year, the flu shot is less effective and more people will get the flu.

Vaccines have done amazing things.  They have eradicated smallpox, a deadly disease that had been around for over 12,000 years and killed 30-35% of people who were infected.  Eradicating this disease saves the lives of over 5 million people each year who would have been infected and died otherwise.  Polio, another crippling disease, has nearly been eradicated with only a few hundred cases in 2012 compared to over 350,000 in 1988. Common childhood diseases like measles and whooping cough have also been decreased considerable, saving millions of lives each year through vaccines.  They are truly a modern medical miracle!