Today, researchers announced that the London patient—the second person ever to be cured of HIV with a bone-marrow transplant—is still living without cancer and without HIV, more than two years after his treatment.
The results of this case study were presented in The Lancet HIV journal and presented at the Conference on Retroviruses and Opportunistic Infections (CROI).
“Our findings show that the success of stem-cell transplantation as a cure for HIV, first reported nine years ago in the Berlin patient, can be replicated,” said lead author Ravindra Kumar Gupta, Ph.D., a professor at the University of Cambridge in the United Kingdom, according to a press release.
But despite the excitement of a second probable cure, Gupta cautioned that bone-marrow transplant is not a realistic path forward for most patients, and is instead “a last resort for patients with HIV who also have life-threatening hematological malignancies.”
The London patient’s HIV remission was first announced one year ago, after he recovered from his cancer treatment and no longer had active HIV in his blood. Now, as researchers have confirmed the durable nature of this cure, the patient himself has decided to come forward.
That patient’s name is Adam Castillejo. After remaining anonymous for over a year, he told The New York Times that he wanted to “be an ambassador of hope” in the ongoing global quest for an HIV cure.
In 2019, researchers reported Castillejo’s HIV remission, although he wasn’t named at the time. Like Timothy Ray Brown, the Berlin patient, Castillejo underwent a successful stem-cell transplant using tissue from a donor who possessed an HIV-resistant gene mutation. After his transplant, Castillejo was able to stop taking daily antiretroviral therapy (ART).
Twenty-nine months after he stopped ART, researchers took samples from his cerebrospinal fluid, intestinal tissue, and lymphoid tissue, performing ultrasensitive viral load testing and finding no active viral infection. One month later, researchers tested Castillejo’s blood and similarly did not find any active viral infection.
The sensitive equipment did detect small bits of HIV-1 inside the tissue samples, but study authors described those as “fossils” that are unable to reproduce or infect new cells.
Researchers also reported that Castillejo had a healthy CD4 count, indicating that he not only was free of HIV, but also that he has recovered from his transplant. As is the goal of a bone-marrow transplant, the vast majority of his CD4 cells (99%) were replaced by donor tissue—in this case, HIV-resistant transplanted stem cells.
Gupta and his colleagues also used a model to predict how likely it is that Castillejo will remain HIV-free for the rest of his life. They estimated that if 80% of the stem cells in his body were from the donor, then he has a 98% chance of being cured for life. But if 90% or more of the cells were from the donor, Castillejo is 99% likely to be fully cured.
Using that model, Gupta feels confident calling this a cure.
“We propose that these results represent the second-ever case of a patient to be cured of HIV,” he said in prepared remarks.
In a commentary accompanying the Lancet HIV publication, Sharon R. Lewin, M.B., B.S., Ph.D., of the University of Melbourne in Australia, said these 30-month findings should reassure Castillejo and his doctors that the virus is unlikely to rebound. However, Lewin, who was not involved in the study, cautioned against the use of the word “cure.”
“In view of the many cells sampled in this case, and the absence of any intact virus, is the London patient truly cured? The additional data provided in this follow-up case report is certainly exciting and encouraging but, in the end, only time will tell,” she wrote in the accompanying commentary.
Ultimately, Gupta and colleagues noted that this case study represents a step forward for this particular cure strategy, because it demonstrates that HIV can be eradicated with one stem-cell transplant rather than two, and without total body irradiation. The only other person to have been cured, Timothy Ray Brown, underwent a more intensive transplant and treatment procedure to treat his cancer.
But researchers also noted that for the majority of patients, this approach is not realistic. Instead, it gives credence to the ongoing efforts to use gene-editing techniques to cure HIV—replicating the results seen by the London and Berlin patients with precise gene-editing tools, rather than by using brute force with a risky bone-marrow transplant.