A recent article in Nature shared the news about a 53-year-old man in Germany who was declared free of HIV after receiving virus-resistant cells.
The man—referred to as the “Düsseldorf patient”—was diagnosed with acute myeloid leukemia and underwent a stem cell transplant in 2013 that replaced his bone marrow cells with HIV-resistant stem cells from a donor.
In the five years following the procedure, virologist Björn-Erik Jensen and his team at Düsseldorf University Hospital in Germany continued to monitor the patient. They continued to find immune cells that reacted to HIV in his body, which suggested that his body was not clear of the virus.
In 2018, the patient stopped taking antiretroviral therapy (ART), a treatment for HIV that reduces a person’s viral load to an undetectable level. His body has remained HIV-free since then, indicating that the stem cell transplant worked.
Similar stem cell treatments have been used to treat others living with HIV, including a patient in 2007 and another patient in 2019.
The Nature article states that the procedure is unlikely to be used widely in its current form because of the associated risks, including the chance that an individual will reject a donor’s marrow.
Scientists continue to test stem cells as a treatment for HIV, including methods in which cells are taken from a person’s own body and genetically modified, eliminating the need for donor cells.
CIRM’s Commitment to Investing in Treatments for HIV
The Düsseldorf patient’s case highlights the need for continued stem cell and gene therapy research for HIV.
At CIRM, we have invested more than $85 million in developing stem cell and gene therapy approaches for HIV/AIDS, from basic discovery through clinical trials.
Recent awards include a UC Davis study that modifies a patient’s T cells so they can recognize and target HIV without ongoing medication. CIRM also funded a UCSF clinical trial using duoCAR‑T cells. In that trial, researchers extract T cells, engineer them with two chimeric antigen receptors, and return them to the patient to destroy HIV‑infected cells.
The goal of this one‑time therapy is long‑term HIV control without ART—a functional cure. It may also help people who cannot benefit from current approaches, a group estimated to include 50 percent of those affected globally.
Last year, UCSF researchers announced they had dosed the first patient in the duoCAR‑T trial.
About 38 million people worldwide live with HIV/AIDS, and an estimated 1.5 million new cases occur each year. Many do not have access to lifesaving antiretroviral drugs. Those who do often face long‑term complications, including heart, liver, bone, and metabolic issues.
Immune system of humans are generally activated in response to the entry of foreign antigen or pathogen. The activation of immune system not only releases a variety of killer cells but also produce different types of cytokines. Different people have different abilities of immunity to destroy the pathogens from invasion. Therefore, results of clinical investigation showed different immune response of patients to one particular antigen. Most of viruses can easily mutate to defend themselves from destroying by immune system. Hence, clinical investigation showed Dusseldorf had ability to survive longer with HIV-free but not for the others. This indicated that HIV can easily mutated to other strains to defense themselves for further replication and growth in host. Gene therapy to modify the adhesion molecules of HIV which is so-called CCR5 into CCR5n32/n32 to prevent CCR5-cell-surface protein from being exposed on the cell surface. This therapy may give some advantage to certain patients but not for others. The HIV virus can easily mutated, sooner or later is very depened on the environment of human body. The mutated HIV can take other entry point rather than CCR5 as usual for replication and growth. The introduction of duoCAR-T cells may provide additional advantage to reduce virus-load of patient’s body. The chimerization of two receptors to produce duoCAR-T cells must take account chimeric TCRs do generate a full signal to kill most of HIV. As TCR complex consists of an alpha-beta heterodimer and noncovalent associated with the CD3-gama-delta-epsilon and zeta. The optimum activation of T cells is dependent on TCR transmitting the signal to CD3/zeta complex, which may triggering phosphorylation of ITAMs to influence several downstream cellular response. Thus, the weak association of chimeric construct may produce suboptimal activity of antiHIV duoCART-cells which may not have lethal effect to HIV particles.