Changing My Genes
Living with AIDS for more than 22 years is a personal accomplishment -- one that I celebrate with my healthcare provider. This achievement has also been a journey that gave me the opportunity to learn more about myself, HIV, my immune system, and other possible treatments through my participation in clinical trials.
I have been very fortunate to receive my HIV care for the last 17 years at the UCLA CARE Clinic. It is not only a clinic that provides the best HIV care in Southern California, but also a research center that conducts trials on HIV treatment, including gene therapy.
When I was diagnosed with AIDS in 1990, like many people I faced the disease with fear and very low expectations of survival. I learned to live one day at a time, and every day I lived was a major achievement. Adding or changing an HIV drug was a way of buying time in the hope that something better would come along. At that time in the epidemic, we did not have long-term goals or dreams to accomplish -- we just worked hard to survive and cope with the severe side effects of the old HIV medications. Since I had nothing to lose but a lot to give, I started participating in clinical trials under the close supervision and advice of my doctor.
In early 2010 I heard about a study of a new treatment called SB-728T being developed by Sangamo BioSciences. It was a Phase I trial -- the earliest study of a new treatment -- designed to examine the safety and tolerability of the treatment. I was told that some of my CD4 cells would be removed and multiplied outside of my body. They would then be treated with a "zinc finger" nuclease that would change their DNA so that they no longer had any CCR5 receptors on their surface (HIV uses CCR5 receptors to enter a cell). With a now different set of genes, these modified CD4 cells would be reinfused into me. The idea was to remove the CCR5 receptor to make these modified CD4 cells resistant to the invasion of HIV.
It is important to note that my CD4 count when I was diagnosed was 90, and it never went above 120 in the decade after my diagnosis. It wasn't until 2005 that it went up to 373. The persistent low count, even after years of standard HIV treatment, was a key factor in helping me decide to enroll in this study.
The process started with a long interview with the study coordinator. She made me aware of all the pros and cons of the study, what to expect, and the exact protocol and timeline of the procedures. The study involved several risks that were explained in detail by the principal investigator. The main risks were side effects as a result of allergic reactions to the chemicals involved in the transfusion of the modified cells. Also, I was told I might have a garlicky body odor for a day or so after the infusion.
Whenever I have been involved in a clinical trial, I've always been fully aware that uncertainty is the key word to keep in mind. The fact is, you never know if the results will be good or bad for you. You lend your body to science and hope for the best. But I do my homework before joining a trial to make sure I think the risks are worth it.
This study is a long-term commitment -- I will be followed for three years. The first battery of tests involved a blood draw of almost twenty tubes for a large number of lab tests. It was like being the drink dispenser at the bar of the "True Blood" TV show! The second visit involved a physical examination and the start of the treatment process. I was there for four hours while blood was removed from my body through an IV, my CD4 cells were separated from my blood, and the remaining blood was re-infused back into me.
The procedure required strict monitoring of my vital signs (temperature, pulse, and breathing). I felt quite tired for a few days afterwards since some of my red blood cells were destroyed in the process of removing my CD4 cells. The next step was a long wait for the laboratory to modify my collected CD4 cells and multiply them in vitro (in the lab). It sounds easy, but imagine the amount of time and resources needed to develop these highly technological procedures.
Finally, the day of the infusion arrived. After eight weeks of anxious waiting, everything was prepared for me to receive my modified CD4 cells, in a sterilized room of the brand-new UCLA hospital -- which is so nice it reminded me of a W hotel. I was excited but also apprehensive and a little fearful. I was welcomed by a group of representatives of Sangamo and the UCLA nursing staff. One Sangamo employee commented on my lab results and how fast my CD4 cells grew. I joked, "Of course they grew fast! They're Mexican CD4 cells, and we Mexicans multiply fast!"
This was an open-label single-dose study (no one got a placebo), so we all knew what we were getting. The trial was designed to look at changes in the CD4 count, and CD4/CD8 ratio, and to see how many of the modified CD4 cells stayed in the body. Nine of us were in the study, and we were divided into groups depending on how many cells were reinfused. I don't know which group I was in -- I only know that I received four out of eight bags of my modified cells.
I was first given some pills to prevent an allergic reaction. Then the bags of my modified CD4 cells were infused. My vital signs were constantly checked to make sure that my temperature and pulse were normal and that I wasn't having any sudden unexpected side effects. The nurses did a great job of keeping me informed about each step in the process, making sure that each bag was infused completely and that I stayed well. I was again warned that I might have a weird garlicky body odor in the next few hours due to the fluids in which the modified CD4 cells were kept.
I'm trying to remember my emotional state at the end of the process. I remember how brave I was. I showed up alone and walked away alone from that experience. Also, I remember thinking, "You are participating in cutting-edge research in the search for the cure, after 20 years of surviving AIDS. Way to go, little Mexican!" It was a weird combination of feelings of achievement and wonder. Why I have been so lucky as to still be here? Thank God I am healthy, productive, and a proactive participant in the search for a potential cure against this stupid virus.
There were ZERO side effects afterwards. The garlic smell was almost nonexistent. In order to help you understand the changes that occurred in my immune system, I'll share my lab results below.
|Normal Range||Before Infusion||1 Week After Infusion||1 Month Later||2 Months Later||21 Months Later|
|CD4 count||500 - 1500||373||693||549||770||520|
|CD4 %||30 - 60%||29%||39%||42%||37%||34%|
|CD4/CD8 ratio||1.0 - 3.7||0.81||1.28||1.51||1.11||1.10|
In short, many of my immune system counts are near normal. The modified CD4 cells successfully transplanted into my immune system, and they expanded and persisted in my blood. In addition, every four months I have rectal biopsies taken to determine if the modified CD4 cells migrated to the gut. According to the researchers, the modified CD4 cells transplanted and persisted in my rectal mucosa.
Being in this study has been a very intense, yet very positive learning experience. Being part of something as big as the search for the cure is a humbling experience. I am extremely lucky to have a group of HIV service providers who are a source of constant unconditional support and whom I trust 100%. And I am fortunate to have a doctor who recognizes the importance of listening to the community and who empowers patients to be active participants in cutting-edge research by educating them about the risks and benefits.
I understand that this study is just the beginning of research about the benefits of modified CD4 cells. I strongly recommend that people with HIV ask their doctors about future clinical trials of this technology. I don't know what the future holds for me, but if I can keep participating in this kind of study, I will. I am convinced that I have been blessed to have more than 20 years of survival with AIDS. Now it's my turn to give back what I have received and hope that we will be able to conquer HIV and defeat AIDS.