HIV-infected T cellFLICKR, NIAIDMost HIV treatments depend on the activation of all CD4+ memory T cells that harbor the latent reservoir (LR), which is composed of inactive HIV proviruses integrated into the genomes of these resting cells. Knowing the size of the LR is essential for measuring the success of antiviral therapies. Two common ways to test for provirus in a patient with HIV are the PCR-based method, in which integrated HIV DNA is amplified and quantified using PCR and the viral outgrowth assay (VOA). For the VOA, a patient’s CD4+ T cells are collected and then activated in vitro, so that they produce virus from the LR and release viral proteins that can then be quantified. PCR detects much more provirus than the VOA, and in the past, it was assumed that not all of the provirus that is detected by PCR is transcription-competent. Now, researchers from Johns Hopkins University School of Medicine in Baltimore, Maryland, have characterized the LR more completely than ever before, and show that its size is perhaps 60 times larger than predicted by the VOA. Their work was published today (October 24) in Cell.
“I think it’s an excellent paper and a very provocative finding,” said HIV researcher Jonathan Karn, a professor of molecular biology at Case Western Reserve University, who was not involved in the work. The evidence “does indicate that the VOA probably underestimates the latent reservoir,” added Karn, which is “really quite an important observation.” Knowing the LR’s true size is essential for clinicians who must decide when a patient can discontinue antiretroviral therapy, he noted.
The VOA “is a very sensitive assay to detect all possible viruses released after maximum T cell activation, so people have believed that this scale of the latent reservoir is what we need to eradicate, which is around one in one million resting CD4+ T cells,” said first author Ya-Chi ...
