February 5, 2001
For the past several years, there has been hope that effective HIV treatment might one day result in the eventual eradication of HIV from the body. However, recent data from this group and supportive work from other studies have shown how daunting, if not impossible, is this task. The key barrier was summarized in this talk that updated us about the reservoir of HIV in the body.
For the past few years it has been understood that HIV lives in several types of cells. Some cells die quickly once HIV starts replicating in them -- this is mainly seen in the CD4 lymphocytes. However, HIV also integrates itself into one of the longest-lived cells in the body -- the resting memory T cell. These cells are designed to live as long as we do (about 73 years) -- as they are the part of the immune system responsible for protecting us for life from all infections we have seen at any point during our lives. These cells go into a resting state after infection by HIV -- and it appears unlikely at best to identify these cells after infection since they show no evidence of HIV infection hiding inside the genes of the cell. Thus, in addition to being long lived, they are also difficult, if not impossible, to target for selective destruction. Of note, there are about one million such cells in the body -- giving rise to a somewhat simplistic notion that we are about one million cells away from defining a route to a cure for HIV infection.
There has been a lot of research focused on defining the time of the natural "decay" of these cells in people on antivirals with consistent viral loads of less than 50 copies -- and in several studies, there is very little if any loss of these cells over time. One reason for this is that if the cell actually does die, it divides and its "daughter" cells will also contain HIV.
However, there was one important and hopeful note in this talk. In studies of these cells -- in people who are doing well, with consistent viral loads on meds below 50 copies, there is no evidence of the evolution of resistance to antivirals in these cells. The reservoir does reflect most, if not all, of the HIV strains that have ever been in the body -- so if someone has had degrees of medication resistance at some point, it is possible and perhaps likely that these resistant strains are "stored" in this cell population. (This gives pause to the potential for "recycling" antivirals after resistance has occurred at any point, as it is predicted that resistant strains will eventually reemerge from this compartment.)
However, for those who have no resistance to medications and are staying below 50 copies, this research shows no evidence of resistant strains hiding in these cells either. This implies that for those doing the best on meds, resistance may be indefinitely prevented as long as viral suppression is maintained. This is true even for those on a medication such as lamivudine to which resistance can occur relatively quickly. Thus, whenever antivirals are initiated, it is at least theoretically possible that they may remain active for as long as needed. Since HIV infection does appear to be a lifelong struggle, it appears it will be necessary to do whatever is possible to maintain the potency from medications.
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