March 14, 2012
The 19th annual Conference on Retroviruses & Opportunistic Infections (CROI) took place last week from Monday through Thursday in Seattle. As has consistently been the case in recent years, the organizers have done a commendable job in making the conference accessible online: all sessions -- including poster discussions -- are available via webcast, and very few presenters have failed to make their slides available.
Research into curing HIV infection featured prominently at the meeting, building on the case of Timothy Brown that was reported for the first time on a poster at CROI four years ago. A symposium on the subject was held from 4-6pm on Wednesday March 7th and featured several excellent overview presentations on the state of the science. The major message that emerged from data presentations on cure-related research was that a one-two punch may be needed to address HIV reservoirs: firstly, dormant HIV in latently infected cells must be awakened and, secondly, effective T cell responses are likely to be required to deliver the coup de grace and kill the HIV-infected cells that are induced to produce virus.
The rationale for this two-pronged approach was encapsulated in presentations by David Margolis from the University of North Carolina and Liang Shan from Johns Hopkins University. Margolis showed that administration the HDAC inhibitor vorinostat (also known as SAHA) successfully induced latently infected cells to express HIV RNA in six trial participants on ART (up from the four participants Margolis was able to discuss last December at the HIV persistence workshop). Liang Shan described laboratory experiments demonstrating that HIV-specific CD8 T cells from individuals with chronic HIV infection are generally unable to kill CD4 T cells that are induced to produce virus by exposure to vorinostat. In many cases, this failure could be overcome by stimulating the HIV-specific CD8 T cells with HIV antigens immediately prior to mixing them with the HIV-infected CD4 T cells, suggesting to Shan and colleagues that therapeutic immunization should be combined with anti-latency drugs (the paper containing these results was published by the journal Immunity on the same day as Shan's CROI talk, click here and scroll down to see the abstract).
Richard Jefferys is the coordinator of the Michael Palm HIV Basic Science, Vaccines & Prevention Project Weblog at the Treatment Action Group (TAG). The original blog post may be viewed here.
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