Researchers’ came up short when they attempted the first-ever randomized trial of an HIV cure method, aidsmap reports. The so-called kick-and-kill strategy did not reduce the amount of viral DNA in participants—an indicator that their viral reservoir was remained in place despite the two-part treatment.
Even when people with HIV have a fully suppressed viral load thanks to antiretroviral (ARV) treatment, they harbor virus in latently infected immune cells, which constitute amajor part of what is known as the viral reservoir. Because these cells are not replicating, they remain under the radar of ARVs, which work only on replicating cells. This phenomenon is the reason why standard HIV treatment does not cure people of the virus.
In recent years, scientists in the HIV cure field have been honing one particular strategy in which they use an agent to prompt latently infected cells to begin replicating again (the “kick”) and another treatment to go after those newly aroused cells (the “kill”). Cancer drugs known as HDAC inhibitors have been investigated to serve as the kick portion of this equation.
Presenting their findings at the International AIDS Conference in Amsterdam (AIDS 2018), researchers from the RIVER study recruited 60 men who had been diagnosed with HIV and put on ARVs within weeks of contracting the virus.
The men had an average age of 32. They had an estimated maximum period between acquiring HIV and being diagnosed with the virus of 16 weeks and a minimum time of 12 weeks on ARV treatment before entering RIVER. The average period between the participants’ contracting HIV and starting the study was 28 weeks. They had an average CD4 count of 708, and all but one of them had a fully suppressed viral load.
The participants were randomized to continue taking their ARVs and no other treatment or to stay on ARVs and receive the kick-and-kill treatment. The treatment involved two shots of a vaccine, given eight weeks apart, that was meant to spur a stronger and more broad immune response to HIV. That was the kill portion. For the kick part, the researchers used the HDAC inhibitor Zolinza (vorinostat), given every three days for the 30-day period after the second vaccine shot.
Those in the kick-and-kill treatment group experienced more adverse health events than those in the control group, although the excess health events were mild. Six people in the control group experienced severe adverse health events, compared with one person in the kick-and-kill group.
In the end, there was no difference in HIV DNA between those in the two study groups, nor was there a difference in the amount of new viruses produced by cells drawn from the participants and studied in a lab dish.
The kick-and-kill regimen’s effects were not nil. Those who received it saw a nearly 10-fold increase in their number of CD4 cells primed to target HIV as well as a smaller rise in such HIV-specific CD8 cells. Additionally, the treatment was associated with an increase in HIV gene expression among the participants; the researchers are investigating the significance of this shift.
To read the aidsmap article, click here.
To read the conference abstract, click here.
To download the conference slides, click here.