HIV remission achieved in second ever patient
The second recorded case of a patient experiencing remission from HIV-1 infection after stem cell transplantation has been reported by UK scientists. The patient has so far been in remission for 18 months, though the authors caution that it is too early to say that the patient is ‘cured’ of HIV.
The first ever patient to be cured, Timothy Ray Brown (also known as the ‘Berlin patient’), was diagnosed with HIV in 1995 and later with acute myeloid leukaemia (AML) 2006. His physician arranged for him to receive a haematopoietic stem cell transplant from a donor with two copies of the Δ32 mutation of CCR5. CCR5 is a co-receptor for HIV-1 infection, and homozygous carriers of the Δ32 mutation are resistant to infection with HIV-1 viruses that use this co-receptor. This resistance was therefore carried by the transplanted cells.
Brown stopped taking his antiretroviral medication on the day of his first transplant and has been considered ‘cured’ ever since, but the treatment was very aggressive and the approach has not been successfully repeated. That all changed when UK researchers, led by Ravindra Gupta from University College London, demonstrated a less aggressive form of this treatment in a patient with HIV-1 who was diagnosed with advanced Hodgkin’s lymphoma in 2012. Their study has now been reported in the journal Nature.
To treat the cancer, the patient received a transplant of haematopoietic stem cells from a donor with two copies of the CCR5 Δ32 allele, experiencing only a mild reaction to the stem cell transplant. The authors reported that the patient became homozygous for CCR5 Δ32 after transplantation, and antiretroviral therapy was interrupted after 16 months. The authors confirmed that HIV-1 RNA was undetectable, and the so-called ‘London patient’ has remained in remission for an additional 18 months.
These findings appear to demonstrate that the Berlin patient was not an anomaly and provide further support for the development of approaches that target CCR5 as a strategy for HIV remission; that’s certainly the impression of Australian and UK experts who have commented on the case. For example, Professor Sharon Lewin, Director of Melbourne’s Peter Doherty Institute for Infection and Immunity, said it was “exciting” that the patient had been in remission for over 18 months, though she said it would be wise to continue closely monitoring his viral load.
“Coming 10 years after the successful report of the Berlin patient, this new case confirms that bone marrow transplantation from a CCR5-negative donor can eliminate residual virus and stop any traces of virus from rebounding,” Prof Lewin said. “Two factors are likely at play — the new bone marrow is resistant to HIV and also the new bone marrow is actively eliminating any HIV-infected cells through something called graft versus host disease.”
Professor Áine McKnight, from Queen Mary University of London, explained the science behind the breakthrough in further detail. She noted that there are two known varieties of HIV — one uses the CCR5 co-receptor and the other uses the CXCR4 co-receptor — with the virus specifically targeting cells of the immune system that use these co-receptors.
“The previous successful study with the Berlin patient employed a technique which can be thought of as an immune system transplant,” Prof McKnight said. “The infected patient’s immune cells were replaced by corresponding ones from an individual resistant to the infection by virtue of the fact that the donor had a mutated form of the CCR5 co-receptor.”
Prof McKnight said people with this mutated form of CCR5 are very rare and, as a consequence, this is only the third study that has attempted to exploit this technique. Furthermore, in all three studies the donor immune cells were of the mutated CCR5 variety, but in the case where the treatment was unsuccessful the recipient was infected with both the CCR5 and CXCR4 strains of the virus. The technique will therefore not necessarily be effective for all HIV-infected individuals.
Dr Sarah Palmer, Deputy Director of the Centre for Virus Research at The Westmead Institute, found the news “encouraging”, saying it “further confirms the promising HIV curative effects of bone marrow transplantation from the relatively few persons who have the HIV-resistant cells known as CCR5/Δ32 haematopoietic stem cells”.
“However, this curative process is not yet applicable to tens of millions of other HIV-infected individuals worldwide,” Dr Palmer noted. “Next steps should be focused on how to do so.”
Professor Anthony Kelleher, Director of the Kirby Institute at UNSW Sydney, added that scientists should exercise caution. On top of the rarity of suitable donors (and the requirement to match them to suitable recipients), and the fact that the procedure itself is not widely available in many countries, there is also a need to assess the cost benefit of a bone marrow transplant versus HIV antiretroviral therapy.
“Finally, there is significant morbidity and mortality associated with this type of transplantation, even when conducted in the best centres, and under the best circumstances,” Prof Kelleher said.
Professor Graham Cooke, from Imperial College London, agrees that the procedure still carries too much risk to be used in patients who are otherwise well, as daily tablet treatment for HIV is usually able to maintain patients’ long-term health. Nevertheless, he said HIV patients needing bone marrow transplantation should be encouraged to consider a CCR5-negative donor if possible.
“If we can understand better why the procedure works in some patients and not others,” he said, “we will be closer to our ultimate goal of curing HIV.”
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