Sizing Up the HIV Reservoir
By Jeffrey Laurence, M.D.
As readers of these bulletins have seen emphasized on many occasions, the primary obstacle to an HIV cure is the persistence of a stable population of HIV-infected CD4+ memory T cells impervious to treatment. amfAR-funded scientists have shown that the magnitude of this “cure barrier” differs markedly among infected individuals depending on several factors. For example, it is significantly smaller in those who begin antiretroviral therapy (ART) within three months of probable infection. Writing in the online journal PLOS ONE, amfAR grantee Dr. Janet Siliciano of Johns Hopkins University now shows how a person’s immune environment while on ART may also impact the size of this HIV reservoir.
Dr. Janet SilicianoWorking under the auspices of the amfAR Research Consortium on HIV Eradication (ARCHE), Siliciano and fellow ARCHE researchers including Drs. Una O’Doherty of the University of Pennsylvania; Sarah Palmer of the University of Sydney and the Karolinska Institute, Sweden; Frederick Hecht and Steven Deeks of the University of California, San Francisco; and Robert Siliciano of Johns Hopkins University, examined the association between HIV reservoir size in blood, assessed by measures of HIV proviral DNA, and markers of T cell activation in 30 HIV-positive adults on ART—10 treated during acute infection and 20 treated during chronic infection. They found a consistent and direct association between the frequency of activated T cells and the frequency of CD4+ T cells bearing HIV DNA across all study subjects.
The authors emphasize that these findings may implicate the activated T cell as a preferential site for HIV infection. They also underscored their significance to one prominent strategy of attacking HIV reservoir cells called “shock and kill.” In this scheme, the silently infected T cells are stimulated to produce virus, then killed by ART. However, “in the absence of effective killing,” Siliciano and associates warn, these reactivation strategies could instead “lead to an increase in reservoir size.”
Dr. Laurence is amfAR’s senior scientific consultant.