A patient HIV-positive bone marrow transplant recipient at the Mayo Clinic has undergone prolonged viral remission lasted almost 10 months - more than the so-called Boston patients - after stopping antiretroviral therapy (HAART), according to a report of the Conference on Retroviruses and Opportunistic infections this month in Seattle. Although viral load possibly recovered, their HIV reservoirs appeared to be reduced.
The only person known to be cured of HIV - Timothy Ray Brown, known as the "Berlin Patient" - stopped antiretroviral therapy when he received a bone marrow transplant to treat leukemia and had no detectable virus for 10 for years. Brown received a transplant from a donor with a double mutation of the CCR5-delta-32, which meant that there was a lack of CCR5 coreceptors, which most strains of HIV use as receptors to enter into T cells. sustained remission is attributable to the donor CCR5 mutation, the strong chemotherapy conditioning regimen used to kill cancerous blood cells, or a graft versus host or multiple factor reaction.
Bone marrow transplantation is apparently not good enough to eradicate HIV. A few years ago, Timothy Henrich reported two HIV-positive bone marrow transplant recipients in Boston who received wild-type donor stem cells without the CCR5-delta-32 mutation that is the receptor from which HIV is used to invade cells CD4 and CD8, who received a milder regimen and experienced acute graft versus host disease (GVHD) transplantation. Both men maintained their undetectable viral load longer than expected after stopping ART, but eventually experienced viral recovery at three and eight months after stopping HIV treatment.
The latest case, filed by Nathan Cummins Mayo Clinic in Rochester, Minnesota, and colleagues, involved a man of 55 years old, who was diagnosed with HIV in 1990 and started combination therapy in 1999 with a score of T cells CD4 cells of 300 / mm3. He stopped the treatment of 2004 and 2009 for unexplained reasonsThen restarted ART consisting of ritonavir, atazanavir boosted (Prezista) plus tenofovir DF and emtricitabine (the drug Truvada).
In April 2013 the man was diagnosed with acute lymphoblastic leukemia B cells in anticipation of chemotherapy, their ART regimen was changed to raltegravir (Isentress), etravirine (Intelence) and tenofovir DF / emtricitabine. In October 2013 suffered reduced intensity conditioning followed by an allogeneic stem cell transplant from a donor wild-type "CCR5".
At the time of transplantation, the major had a viral load of HIV 25 copies / mL and a cell count CD4 288 cells / mm3, and he remained on antiretroviral therapy without interruption. After transplantation, developed opportunistic infections (septicemia by E. coli and Pneumocystis pneumonia) and GVHD experienced the 4 months post-transplant.
The man continued for more than ART 2 years after transplantation, especially with detectable levels of plasma viral load. The RNA of HIV was also undetectable in intestinal biopsy samples. The DNA of HIV in their peripheral blood cells became undetectable until day 56, and repeated leukapheresis procedures showed significant reductions in the size of the reservoir RNA and DNA of HIV.
Furthermore, human anti-HIV antibody levels decreased as indicated by bands of weaker Western blot. However, a single genome sequencing and phylogenetic analysis identified HIV clones identical to 142º day, possibly due to homeostatic proliferation, replication or latently infected cells while it had GVHD.
After HIV levels as low for a long time, the man underwent an interruption of the analytical treatment or carefully monitored interruption of ARV. The plasma levels of HIV RNA were tested every week during the first 2 12 weeks of discontinuation of ART, and then every 4 weeks.
On the 288 day - 9,6 months after stopping HAART - there was a low level viral rebound for 60 copies / ml (in Brazil the tests are sensitive up to 40 copies per ml) of the T. This increased to 1640 copies / mL per day 293, requiring him to resume treatment of HIV with ART. The man had no evidence of drug resistance and his viral load was re-suppressed within a month.
"Allogeneic peripheral blood stem cells in the context of HIV infection is associated with significant reductions in the size of the HIV reservoir in multiple steps, including prolonged remission without HAART treatment," the researchers concluded.
They add that the stem cell transplantation in the deleted viral replication scenario may be associated with loss of specific HIV immune and hypothesis that "immune activation in GVHD configuration without anti-HIV specific immunity may cause homeostatic proliferation of cells latently infected, reducing the chance of eradicating HIV
Written by Liz Highleyman for Aidsmap Translated by Mara Macedo