Leaving No Stone Unturned

Innovation Grants totaling $2 million give life to promising, early-stage cure research

In February, amfAR awarded the first round of new Innovation Grants designed to spur innovation by supporting novel ideas based on limited preliminary data.  Each of the 11 projects addresses one or more of the four key challenges related to persistent reservoirs of HIV that must be resolved in order to develop the scientific basis for a cure.

Among the grantees is Dr. Marta Massanella of the University of California, San Diego, who is studying a recently discovered subset of memory CD4 T cells called Tscm. Several characteristics of these cells, including their ability to produce identical copies of themselves, have led to the hypothesis that they may contribute to an ever increasing proportion of the reservoir over time. Understanding which cells the reservoir hides in, and how the relative contributions of each subset may change over time, will help researchers design interventions specifically targeting the reservoir cells.

The amount of virus in the reservoir differs among infected people due to a number of factors, including how soon after infection a person starts treatment. Dr. Satish Pillai of Blood Systems, Inc., San Fransico, California, and his colleagues believe they have identified another factor that influences reservoir size, namely the amount of two specific antivirus factors (p21 and schlafen 11) present inside a person’s cells. Pillai and his team will study the relationship between levels of the two factors and the amount and degree of latent virus inside infected cells. Their findings could inform methods for determining the size of the reservoir, and may constitute a pathway for the development of anti-latency drugs.

One of the challenges facing the so-called “kick and kill” (or “shock and kill”) strategy for curing HIV is the inability of “kicking” compounds to reach all infected cells. This means that even under optimal conditions, latent proviruses inside some infected cells remain dormant and cannot be attacked by antiretroviral drugs or the immune system. Dr. Vicente Planelles of the University of Utah plans to characterize the differences between viruses that can be induced and those that cannot. Understanding why some viruses resist “kicking” will help researchers hone strategies to ensure that all viruses can be activated, leading to the total elimination of the infected cells.

“This round of Innovation Grants represents amfAR’s continued commitment to looking for answers on every scientific front, to spur discovery, and ensure that no potential breakthrough or advance goes unfunded,” said amfAR Vice President and Director of Research Dr. Rowena Johnston.