Researchers report positive bone marrow transplant case
An HIV-positive bone marrow transplant recipient at the Mayo Clinic experienced prolonged viral remission lasting nearly 10 months – longer than the so-called Boston patients – after interrupting antiretroviral therapy (ART), according to a report at the Conference on Retroviruses and Opportunistic Infections (CROI 2017) last month in Seattle.
ALTHOUGH his viral load eventually rebounded, his HIV reservoirs appeared to be reduced. The only person known to be cured of HIV — Timothy Ray Brown, known as the ‘Berlin Patient’ — stopped ART when he received a bone marrow transplant to treat leukaemia and has not had detectable virus for 10 years. Brown received a transplant from a donor with a double CCR5- delta-32 mutation, meaning they lack the CCR5 co-receptors most types of HIV use to enter T-cells.
It is unclear whether his sustained remission is attributable to the donor’s CCR5 mutation, the strong chemotherapy conditioning regimen used to kill off cancerous blood cells, a graft-versushost reaction or multiple factors.
Bone marrow transplantation is apparently not sufficient to eradicate HIV.
A few years ago, Timothy Henrich reported on two HIV-positive bone marrow transplant patients in Boston who got stem cells from ‘wild-type’ donors without the CCR5- delta-32 mutation, received a milder conditioning regimen and experienced acute graft-versushost disease (GVHD). Both men maintained undetectable viral load longer than expected after interrupting ART, but eventually they experienced viral rebound at three and eight months after stopping HIV treatment.
The latest case, presented by Nathan Cummins of the Mayo Clinic in Rochester, Minnesota, and colleagues, involved a 55-year-old man who was diagnosed with HIV in 1990 and started combination ART in 1999 with a CD4 T-cell count of 300 cells/mm3. He stopped treatment between 2004 and 2009 for unexplained reasons, then restarted ART consisting of ritonavir-boosted atazanavir (Prezista) plus tenofovir disoproxil fumarate (DF) and emtricitabine (the drugs in Truvada).
In April 2013 the man was diagnosed with B-cell acute lymphoblastic leukaemia.
In anticipation of chemotherapy, his ART regimen was switched to raltegravir (Isentress), etravirine (Intelence), and tenofovir DF/emtricitabine. In October 2013 he underwent reduced intensity conditioning followed by an allogeneic stem cell transplant from a CCR5 ‘wildtype’ donor.
At the time of transplantation the man had an HIV viral load of 25 copies/ ml and a CD4 count of 288 cells/mm3, and he stayed on ART without interruption. After the transplant he developed opportunistic infections (E. coli septicaemia and pneumocystis pneumonia) and experienced GVHD at four months post-transplant.
The man continued on ART for more than two years after transplantation, mostly with detectable plasma viral load levels. HIV RNA was also undetectable in gut biopsy samples. HIV DNA in his