What all the different approaches discussed in the previous report have in common is to put HIV infection into persistent remission, but they do not completely remove HIV from the body. But in what is still the one case of a person cured of HIV, that is what was achieved; researchers have not managed to find any trace of HIV in the body of Timothy Ray Brown (who attended a symposium presenting the main data from the Cure and Cancer Forum) nearly a decade after he was cured.
A cancer patient, Brown’s cure involved a hazardous bone marrow transplant that made him very ill and left him with some permanent nervous system damage. Nonetheless, experiments continue to induce the complete removal of HIV using similar transplant technology in patients with cancer and HIV.
In the HIV Cure and Cancer Forum (held before the IAS 2017 conference), Maria Saldago of the IrsiCaixa AIDS Research Institute near Barcelona in Spain presented results from ICISTEM, a cohort of patients with HIV and advanced cancers (mainly leukaemia and lymphoma) who have had bone marrow transplants. As such patients are rare, ICISTEM has only collected data on 23 patients, 11 of whom have died.
Salgado presented data on the six patients in the remaining 12 who have had more than two years’ follow-up.
In five of these six patients, the HIV-free bone marrow stem cells rapidly replaced their cancerous and HIV-infected lymphocytes. Ultrasensitive tests can find no HIV RNA in their blood – their viral load, in short, approaches zero – and can also find no HIV DNA in their reservoir cells. In some patients, HIV undetectability in reservoir cells happened within a month; in others, HIV levels slowly declined over a period of up to a year.
The key to full replacement by new cells appeared to be graft-versus-host disease (GvHD), a condition in which the grafted bone marrow cells ‘reject’ the body’s own cells as foreign – essentially the reverse of what happens in typical transplant rejection. This is normally a condition transplant doctors try to avoid, as it creates severe and in some cases lethal inflammation.
In the case of these patients, and in Timothy Ray Brown, GvHD appears to have been an essential part of the process whereby their HIV-infected immune system may have been replaced by a non-infected one. In fact, it may be the essential step: although Brown was transplanted with cells from a donor who was naturally immune to HIV, only six out of the 23 ICISTEM patients have received cells from HIV-immune donors.
Are the ICISTEM patients cured? We don’t know. Although the researchers have failed to find a single copy of HIV DNA in one million resting reservoir cells in some of the patients, the test will be to take these patients off antiretroviral therapy (ART). We have had disappointments before, as when HIV reappeared, after a delay, in the so-called ‘Boston patients’ even though their DNA became completely undetectable.
Salgado told the Cure and Cancer Forum that treatment interruptions were planned for early next year. Then we will find out if Timothy Ray Brown finally has company.