Growing up in Manhattan, Nathalia Holt interned at a hospital in Hell’s Kitchen as a teenager in the 90s. It had a really large AIDs ward. “As a teenager it really touched me, it stayed with me.” She almost always knew she wanted to be a scientist and ended up majoring in molecular biology in college and then earning her PhD. She completed her dissertation on HIV gene therapy. Holt is an award-winning research scientist specializing in HIV biology. She trained at the Ragon Institute of Massachusetts General Hospital, MIT and Harvard University, the University of Southern California and Tulane University. CURED is about the Berlin patients, two patients diagnosed with HIV who became cured through two vastly different treatment plans.
Amy Steele: Why did you want to write this book?
Nathalia Holt: I was really struck by how few people had heard of the Berlin patients. It’s such a big story for HIV researchers and those living with HIV. It’s a great. I really wanted to bring this story about somehow. It’s a story you’d not expect.
Amy Steele: Can you explain the Berlin patient?
Nathalia Holt: There are two Berlin patients. One of them [known by the identity Christian Hahn] received this really aggressive therapy from a family doctor in Berlin. And he got cleared of the virus and his case has inspired a lot of cases of eradication of the virus using early aggressive therapies. The second Berlin patient who is Timothy Ray Brown had cancer and HIV. He was given a stem cell transplant from a person who is naturally resistant to HIV. There’s this small group of people who are naturally able to control their HIV because they have a gene mutation that locks HIV out of their cells. So once he got this stem cell transplant it cleared HIV out of his body. He’s inspired many clinical trials, most prominently, gene therapy trials that have a lot of promise right now.
Nathalia Holt (photo by Steph Stevens)
Amy Steele: How are the Berlin cases important to and the importance to HIV research?
Nathalia Holt: These cases have changed how HIV cases are funded. Cases are directly cited. Last December $100 million grant by Obama for HIV research [ HIV Cure initiative in honor of the 25th World Aids Day launched by Obama administration]. These cases have changed the culture of talking about HIV research and have opened up the funding and way to collect data. Funding agencies that never would have funded before now cite these cases. They’ve changed the culture. They’ve ended up influencing some really big cases. In Timothy’s case, there’s gene therapy in recreating mutations in people’s own cells which may really work. And now we have these pediatric cases. Treat HIV early and aggressively and clear the virus early of these kids. It’s a matter of getting the testing and formulations and bringing it to a bigger scale.
Amy Steele: You’ve said that the medical community and researchers don’t like to talk about a cure. You talked about the difference between a functional and a sterilizing cure and yet you titled your book CURED. Why?
Nathalia Holt: Previously you didn’t want to talk about a cure. It had a terrible reputation. It’s completely changed now. I was at a big HIV meeting last week and there was a Cure symposium. It’s really such an incredible turnaround. When I think about five years ago at the same meeting and what it’s like today, it could not be more different. People are very comfortable using this cure word when talking about HIV. And I feel very comfortable talking about these patients being cured.
Amy Steele: What makes a retrovirus?
Nathalia Holt: It’s made of RNA. How they’re really sneaky is that they can integrate into our own DNA. They package their own genetic material and hide it in our genetic material. They basically turn our cells against us and make a virus that way. It’s why it’s so difficult to treat [HIV]. It is able to hide so well in the body.
Amy Steele: You said that the gut not the blood contains “vast majority of the body’s immune system, more than 70 percent of all T cells reside there not in our blood.” How is this important?
Nathalia Holt: For so many years people were focused on the blood because it’s so much easier to sample the blood and filter the blood. Yet this is the tissue where you have all these cells that HIV loves that are all packed together. And you also have these long-lived cells in the gut for HIV to hide. So it’s important to remember these anatomical sites that you wouldn’t consider otherwise.
Amy Steele: How is gene therapy more effective than other types of therapy? Can you explain the importance of the CCR5 gene?
Nathalia Holt: You can draw blood from a person with HIV and then you can isolate out the cells and make cuts in the CCR5 gene, the same gene that people who have this mutation this gives them a natural resistance (to HIV). And because they have this mutation in this gene, HIV can’t enter their cells. So after you modify their cells you’re able to put them back into the same patients and they hone to the body, to the bone marrow and become part of this next generation of cells that are resistant to HIV. And more than that they have a selective advantage.
Amy Steele: You did a great job describing the personal lives of the Berlin patients are. Sounds like Timothy’s doing a lot of speaking engagements.
Nathalia Holt: He’s doing much better. He has a new living situation and a new boyfriend. He’s so much better and so much happier.
Amy Steele: He had so many other things going on besides HIV.
Nathalia Holt: He had three rounds of chemo. He had kidney failure. It’s just the toll of having multiple brain biopsies, a stem cell transplant. I think anyone would be knocked down for a while. It’s good that he’s coming back now and feeling better.
Amy Steele: Both Christian Hahn and Timothy Brown still consider themselves to be HIV positive although essentially cured of it.
Nathalia Holt: I really thought this was an interesting thing. Somehow having the virus has this identity of its own.
Amy Steele: One thing I took away from the few semesters of nursing school and becoming a medical assistant is that every medication has side effects and no medication is 100% effective. It’s intriguing in any study how individual it becomes.
Nathalia Holt: These physicians tailored therapy just for them and not for anyone else. It was made very thoughtfully by their physicians. And it says so much for primary care.
purchase at Amazon: Cured: How the Berlin Patients Defeated HIV and Forever Changed Medical Science
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