Two people with HIV who received stem cell transplants for the treatment of lymphoma are now controlling HIV replication without medication in the early weeks of treatment interruption, following the discovery that both had experienced loss of detectable HIV DNA, researchers from Boston reported on Wednesday at the 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Kuala Lumpur, Malaysia.
Although the treatment patterns of the two patients bear some similarities to the 'Berlin patient' who experienced a 'functional cure' of HIV infection after aggressive chemotherapy, immunosuppressive treatment and a bone marrow transplant from a donor with genetic resistance to HIV the 'Boston patients' also differ in several respects, which could provide important clues about how remission from active HIV infection could be achieved in other people with longstanding HIV infection.
The findings were reported by Timothy Henrich of Brigham and Womens Hospital, Boston, who has led the team conducting extensive tests on the patients. They concern a small group of people with HIV who were evaluated after hematopoietic stem cell transplants for lymphoma at hospitals in Boston (transfer of stem cells that will replace all blood cells, derived the from genetically matched donors). Three patients were originally evaluated but one died of recurrent Hodgkin's lymphoma six months after the transplant.
Both the surviving patients had been receiving prolonged antiretroviral therapy and received stem cell transplants with a reduced-intensity conditioning regimen of chemotherapy designed to eradicate the cancer and eliminate the existing bone marrow. In the case of the two patients under investigation, the conditioning regimen did not include radiotherapy and it did not eliminate the residual lymphocyte population. In contrast, the 'Berlin patient' received a much more aggressive regimen which eliminated existing bone marrow cells.
The transplants also differed from the 'Berlin patient' because they did not come from donors with genetic resistance to HIV infection (a CCR5 delta 32 mutation), so the cells were susceptible to HIV infection.
Measurements of HIV DNA showed that, around 200 days after transplant, HIV DNA levels had declined below 50 log copies per million PBMCs (peripheral blood mononuclear cells, part of the immune system) in one patient, while HIV DNA fell below this level around 280 days after transplant in the other patient. In both cases, HIV DNA levels have continued to decline after this point. After transplantation, the two patients have been followed for 21 (patient A) and 42 months (patient B), respectively.
More sensitive HIV DNA testing using larger samples of blood obtained by leukapheresis and rectal tissue biopsy showed that HIV DNA was below the limit of detection in both patients. Patient A provided a sample of 25 million PBMCs, and testing with a limit of detection of 0.07 copies per million PBMCs failed to detect HIV DNA. Patient B provided a sample of 50 million PBMCs, and testing with a limit of detection of 0.01 international units per million PBMCs similarly failed to detect HIV DNA.
Viral co-culture from CD4 lymphocytes failed to detect HIV in either patient. A rectal biopsy in patient B failed to detect HIV DNA in rectal cells that would be expected to provide a reservoir for HIV (limit of detection 2 copies per million cells).
After establishing that HIV DNA could not be detected, the researchers conducted extensive discussions with the patients and healthcare providers over a six-month period about the acceptability of an experimental treatment interruption in order to test viral control off medication.
Both patients consented after review of the study protocol by an internal review board. The patients are now being intensively monitored with weekly viral load (RNA) tests and bi-weekly testing of HIV DNA in PBMCs and, after six to eight weeks, the patients gave large volumes of blood for more sensitive analysis of HIV DNA. Leukapheresis will be repeated every three months.
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Two stem cell transplant recipients now controlling HIV off treatment
