Patient With HIV After Bone Marrow Transplant Off ART For 288 Days Without Rebound
A viral remission in a bone marrow transplant HIV-positive recipient lasting nearly one year. Such a timeframe is longer than in the so-called Boston patients.
This case presented by Nathan Cummins of the Mayo Clinic in Rochester, Minnesota, and colleagues at the Conference on Retroviruses and Opportunistic Infections in Seattle last month. The experiment involved a man who was diagnosed with HIV in 1990 and started antiretroviral therapy in 1999 with a CD4 cell count of 300 cells/mm3. The patient stopped treatment between 2004 and 2009 for unexplained causes, then restarted ART with Truvada.
In April 2013 the patient was diagnosed with B-cell acute lymphoblastic leukaemia. His ART regimen was switched to etravirine (Intelence), raltegravir (Isentress), and tenofovir DF/emtricitabine. In October 2013 he underwent reduced-intensity conditioning followed by an allogeneic stem cell transplant from a CCR5 'wild-type' donor.
At the time of transplantation, the man stayed on ART without interruption. After the procedure, he developed opportunistic infections – pneumocystis pneumonia and E. coli septicaemia and experienced 'graft versus host disease' condition at four months after transplant.
The man remained on ART for about two years after transplantation, chiefly with detectable plasma viral load levels. HIV DNA became undetectable by day 56 in his peripheral blood cells and replicated leukapheresis procedures showed meaningful reductions in HIV RNA and DNA reservoir size.
At day 288 – 9.6 months after stopping ART – he was found to have low-level viral rebound to 60 copies/ml, raising to 1640 copies/ml by day 293. The man had no evidence of drug resistance, and his viral load was re-suppressed by ART within one month.
"Allogeneic blood stem cell transplantation in the context of HIV is associated with meaningful cuts in HIV reservoir size by various measures, including prolonged ART-free remission," the researchers assumed.
The world remembers another HIV-positive man with bone marrow transplant – Timothy Ray Brown, known as the 'Berlin Patient'. He is the only person is known to be cured of HIV. His doctor, Gero Hutter, cancelled ART when Timothy received a bone marrow transplant to treat leukaemia. For more than ten years after the procedure, Timothy Ray Brown has not had a detectable virus. He received a transplant from a donor with a double CCR5-delta-32 mutation. These co-receptors most types of HIV use to enter T-cells. Mutation in CCR5-delta-32 means lack of possibility to most types of HIV to enter the T-cell.