"London patient" recovered
Doctors confirmed the complete deliverance of the "London patient" from HIV
Polina Loseva, N+1
Doctors found no traces of HIV in the patient's body for 30 months after the bone marrow transplant. This is the second time in history that a stem cell transplant has been able to cure a person of HIV. The decisive factor, apparently, was the complete replacement of the patient's own T-lymphocytes with donor ones. The report is published in The Lancet (Gupta et al., Evidence for HIV-1 cure after CCR5Δ32/Δ32 allogeneic haemopoietic stem-cell transplantation 30 months post analytical treatment interruption: a case report).
Until recently, a person who met with the human immunodeficiency virus had only two possibilities – to get infected and take antiretroviral drugs all his life to contain the infection, or not to let it into his cells. Resistance is determined by the CCR5 gene – it encodes a protein on the surface of lymphocytes, with which the virus binds before penetrating inside. If a small section is missing in this gene (this mutation is called CCR5Δ32), then the protein turns out to be defective, the virus does not attach to it, and the person does not get infected.
In 2007, it turned out that there is a third way – to acquire resistance together with other people's lymphocytes. A patient named Timothy Ray Brown (who is known as the "Berlin patient") was transplanted hematopoietic stem cells from a donor with the CCR5Δ32 mutation, and three years later it turned out that HIV was no longer in Brown's body. However, doctors were in no hurry to repeat this procedure on other patients: red bone marrow transplantation involves many risks, and most often it is much safer for a person to continue standard HIV therapy.
In March 2019, doctors reported that another patient probably repeated the fate of Timothy Brown: he was dubbed the "London patient". The "London patient" had been HIV-infected for almost a decade when he was diagnosed with stage four Hodgkin's lymphoma. Doctors quickly managed to find several bone marrow donors suitable for him – and one of them turned out to be a carrier of the CCR5Δ32 mutation. Almost a year and a half after the transplant, when the patient's lymphoma was cured, doctors found that the vast majority of lymphocytes in the patient's blood were donated, that is, resistant to infection. As part of the experiment, the patient stopped taking antiretroviral therapy, and since then doctors have been closely monitoring his health.
By March 2019, the London patient had been living for a year and a half without drugs for HIV infection, but no one dared to draw unambiguous conclusions - too little time had passed after the transplant. Now another year has passed: the "London patient" told The New York Times the story of his treatment, and his doctors – Ravindra Kumar Gupta from Cambridge University together with colleagues – published their observations of his condition.
Within 30 months after transplantation, doctors analyzed samples of blood, semen, cerebrospinal fluid, as well as biopsies of lymph nodes and intestines of the London patient. Viral genomes could not be found in biological fluids. The sensitivity limits of the analysis do not allow us to unequivocally conclude that there is not a single viral particle in the patient's body anymore, however, if they remain, then in trace amounts. The number of T-lymphocytes, which decreases during HIV infection, has grown and approached the values before transplantation. In some of them, the researchers found remnants of viral genomes – less than 2-3 per million cells – but this result may turn out to be false positive.
Dynamics of recovery of a London patient. Horizontally – days, the date of stem cell transplantation is taken as zero. Red is the percentage of donor T-lymphocytes in the blood, lilac is the number of CD4 lymphocytes in the blood, blue is the number of copies of viral RNA in a milliliter of blood, purple is the number of copies of viral DNA per million blood cells. Here and below are the drawings from the article by Gupta et al.
According to the authors of the article, the disappearance of HIV from the body could be the result of two processes: a reduction in the number of infected cells (i.e., the patient's own T-lymphocytes) or a reduction in the potential reservoir (i.e., not yet infected T-lymphocytes). To guess which process helped the patient recover, the doctors used a mathematical model that predicts the chance of getting rid of HIV depending on the duration of remission (which reflects the number of infected cells) and the number of donor cells (reduction of the reservoir).
According to the analysis using the model, if a person's T-lymphocytes are unstable (that is, they can be infected), but remission lasts 30 months, the chance of recovery is 38 percent. The doctors found 99 percent chimerism in the "London patient", that is, almost all the T-lymphocytes they found were donor and resistant. In such a situation, the model predicts recovery with a chance of almost 100 percent. Thus, the reduction of the reservoir for the reproduction of the virus turned out to be a more significant factor than the duration of remission and the number of infected cells.
The chances of full recovery (vertically) depend on the duration of remission (horizontally) and the percentage of chimerism.
Based on their observations, the attending physicians concluded that it is now possible to talk about a complete recovery of the "London patient" from HIV. Nevertheless, they promise to check his body for the presence of the virus twice a year for the next two and a half years and once a year for another five. At the same time, they note that it is too early to switch to the widespread use of such transplants on humans. The most convenient method, in their opinion, could be editing the genome of patients' own hematopoietic cells, but the safety of this method has not yet been fully studied (as the first clinical trial showed, its effectiveness also remains controversial).
In 2019, scientists told about several more patients who could repeat the success of the "London" and "Berlin", but nothing is known about their fate yet. But it is known that bone marrow transplantation can in rare cases lead to the appearance of donor cells in the patient's sex glands.
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