September 12, 2018
The major reservoir of HIV that persists despite ART is contained in long-lived memory CD4 T cells. Whether other cell types, particularly macrophages, can harbor a reservoir of replication-competent HIV -- and thus contribute to viral load rebound if ART is interrupted -- remains uncertain, and a matter of some controversy among scientists. The question is important, because identifying and eliminating virus reservoirs is a central plank of the research effort to cure HIV infection. In a new paper in the Journal of Clinical Investigation (available open access), Abraham J. Kandathil and colleagues investigate whether human liver macrophages -- which they note comprise up to 90% of all tissue macrophages -- can sequester infectious HIV in people on ART.
The researchers obtained liver tissue samples from eight people with HIV on ART who had undetectable viral loads in blood (seven were undergoing liver transplantation, and one was sampled at the time of death). HIV DNA could be detected in most samples, but it wasn't possible to assess whether this represented unintegrated or integrated DNA in the liver macrophages due to the limited numbers of cells available.
Importantly, in only one case could infectious HIV be propagated from purified liver tissue macrophages into susceptible target cells, leading to the detection of HIV RNA. This individual had been on ART for the shortest period prior to sampling (8 months) and also represented the only instance in which low-level contamination by T cells was detectable in the liver macrophage sample.
The findings suggest that tissue macrophages may not represent a significant contributor to the long-term reservoir of replication-competent HIV in people on ART. The authors suggest several reasons why that might be the case, including expression of the HIV restriction factor SAMHD1 in this cell population and the lifespan of HIV-infected macrophages, which could conceivably cause them to decay much faster during ART than memory CD4 T cells.
Several possible caveats to the study are also noted, such as the relatively small number of participants and the possibility that inflammatory liver disease (which had prompted the need for transplantation in most cases) influenced that makeup of the liver macrophage population, i.e. increasing the number of recently-generated versus longer-lived macrophages.
Despite these limitations, the study adds novel evidence to the debate regarding the role of macrophages in HIV persistence.
Richard Jefferys is project director at Treatment Action Group (TAG).
[Note from TheBodyPRO: This article was originally published by TAG on Sept. 12, 2018. We have cross-posted it with their permission.]
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