A seventh remission, and a gentler road to it

The small, exclusive club of people cured of HIV has just admitted a member with an unusual qualification. In a report published in Nature on 2 December, clinicians describe a 60-year-old man in Germany who has achieved sustained remission from HIV after a stem-cell transplant for leukaemia, the seventh documented case of its kind. What makes the case different from the six before it is the genetic detail: his transplanted cells carried only one copy of the mutated CCR5 gene, the alteration that blocks the virus’s entry into immune cells, rather than the two copies used in every previous remission. If the finding holds, it changes the practical arithmetic of one of medicine’s most famous cures.

The history is short and well known. A handful of patients, beginning with the Berlin patient in 2008, have been treated for blood cancers with stem-cell transplants from donors who are homozygous for a mutation in CCR5, the co-receptor HIV uses to enter T cells. Without the receptor, the virus cannot infect the transplanted immune system, and the patients have remained free of detectable virus, in the most famous cases for over a decade, without antiretroviral drugs. The results are remarkable, but the method has always carried a forbidding limitation: donors with two copies of the mutation are rare, found in perhaps one per cent of people of European descent, and the tissue-type matching required for transplant narrows the field further. The cure has existed, but it has been hard to reach.

The new case relaxes that constraint in a specific way. The patient received cells with a single copy of the mutation, heterozygous rather than homozygous, and the team argues that the protective effect can still be sufficient when the transplant is accompanied by the immune system rebuilding that occurs after the procedure. If a single copy proves adequate, the pool of eligible donors expands dramatically: heterozygous carriers are far more common than homozygous ones, perhaps forty or fifty times more so in European populations, which would make the matching problem, still difficult for any transplant, substantially easier for the specific combination of cancer therapy and HIV remission.

The report is a case study, and case studies carry their own discipline. Sustained remission in one patient, however well documented, does not establish a general result, and the mechanisms by which a single copy of the mutation confers protection need to be worked out rather than assumed. The team is careful to describe what was measured and what remains to be confirmed, and the wider field will be watching whether the pattern recurs. But the direction is significant for exactly the population that a cure must reach: older patients, like this man, are precisely the ones for whom the rigid matching requirements of the earlier approach were most punishing.

The seventh case is, in the fullest sense, a step rather than a conclusion. The Berlin patient’s result proved that a cure was possible; the cases since have been proving that the path to it need not be as narrow as the first one suggested. A cure that requires a rare double mutation in a well-matched donor is a miracle with a waiting list. A cure that can use the far more common single copy is closer to a procedure, and procedures, unlike miracles, can be planned for.