August 28, 2013
Investigators from Boston had previously reported the loss of detectable peripheral blood HIV-1 reservoirs in two individuals following reduced-intensity conditioning allogeneic hematopoetic stem cell transplantation (HSCT) to treat their lymphoma. The investigators' presentation at IAS 2013 completes the picture, with a report that no HIV-1 DNA was detected from PBMCs -- indicating at least a 3 to 4 log10 decrease in peripheral viral reservoir size post-transplantation.
No HIV-1 p24 antigen was detected by viral co-culture from purified CD4+ cells, and no HIV-1 DNA was detected in rectal tissue. Residual host cells constituted less than 0.001% of PBMCs post-HSCT -- and that small detected amount may have represented circulating non-hematopoietic cells. No HLA-specific or pooled HIV-1 peptides elicited a strong HIV-specific immune response from the patients, either before or after allogeneic or autologous HSCT.
These patients have now stopped their antiretroviral treatments with no ill effects. As of the IAS 2013 presentation, one had been off medication for 15 weeks and the other for seven. Neither had any trace of HIV DNA or RNA in his blood.
Obviously, we will need to wait for one or two years before saying with any degree of confidence that these two men are "cured," but data are very reassuring, as HIV-1 rebounds are usually spotted after one week of stopping antiretroviral treatment, particularly when sensitive assays are undertaken.
The two Boston men differ from the cured Berlin patient in two important ways. One, they had lymphoma, while the Berlin patient had leukemia. And two, of importance, they underwent reduced-intensity conditioning allogeneic hematopoetic stem cell transplantation (RIC-alloHSCT) with stem cells from donors who did not have the CCR5 delta 32 mutation (unlike the Berlin patient).
Regardless, this information is a step ahead from the functional cure of the Berlin patient. Now we know that transplanting CCR5-defective bone marrow is not essential for HIV-1 eradication, which will help simplify the equation (which still involves whole body radiotherapy, chemotherapy, immunosuppressive drugs and a stem cell transplant).
While the approach with the Berlin patient carries roughly a 40% risk of death, the Boston tactic carries a lower (15% to 20%) death risk. It is obviously still not a strategy to be widely recommended, but these cases teach us important lessons to learn how HIV can be purged from its reservoirs.
Which other studies presented at IAS 2013 will have lasting impact long after memories of the conference itself have faded? Read more of Dr. Llibre and Dr. Young's top picks.