Aiming to come up with a solution, in June amfAR awarded a $672,000 grant to a research team led by Dr. Timothy Schacker of the University of Minnesota, Minneapolis. Dr. Schacker will collaborate with a pair of leading investigators at the amfAR Institute for HIV Cure Research, Drs. Steven Deeks and Mike McCune of the University of California, San Francisco.
Currently, the most definitive method of gauging whether someone has been cured involves taking the subject off antiretroviral therapy (ART) and determining whether virus grows -- rebounds -- in the blood, indicating that replication-competent virus remains in the person's body. The key question is: How long does it take for virus rebound to occur? And can we find some biological predictor of rebound?
Rebound may take weeks to months--or even years, as was the case in the Mississippi child. The longer it takes for the virus to rebound, the closer the intervention is likely to have come to curing the patient.
While waiting to see if the virus starts to grow, blood must be drawn frequently and tested for the presence of HIV, which is both expensive as well as time-consuming and arduous for the patient. Ideally, scientists should be able to measure something in the blood or tissues that will indicate whether a patient is cured, without having to take the patient off ART.
Drs. Schacker and Deeks will lead a study aimed at discovering such a measure. They will enroll patients on ART and take samples of blood and tissues before taking them off treatment. With ART stopped and while waiting for virus rebound, they will take multiple blood samples and test them for the presence of the virus.
The Mississippi Child
In March 2013, Dr. Deborah Persaud of Johns Hopkins Children’s Center in Baltimore, an amfAR grantee, detailed the case of a 2-year-old child in Mississippi diagnosed with HIV at birth and immediately put on treatment. At 18 months, the child ceased taking ART and was lost to follow-up. When brought back into care at 23 months, despite being off treatment for five months, the child was found to be free of the virus. A battery of subsequent highly sensitive tests was unable to find any HIV. Finally, in July 2014, after being off ART for more than two years without evidence of HIV, researchers determined that the virus had rebounded.
Once HIV becomes detectable in the blood, the patients will restart ART and intensive blood and tissue sampling will be performed again. The researchers will look for indicators in the blood and tissues that predict a longer delay to rebound. They will investigate factors such as the extent to which virus is actively replicating, the size of the reservoir, and gender.
"This is a complex but enormously important study," said Dr. Rowena Johnston, amfAR's vice president and director of research. "If successful, it will provide researchers with an indispensable tool for gauging the success of potential cure interventions.”
Announced in June, the new grant was awarded under the auspices of ARCHE, the amfAR Research Consortium on HIV Eradication. The consortium was established in 2010 as a means of promoting multi-site collaboration on cure-focused research.