Effect of IL-2 in Dimunition of a Pool of Latently Infected, Resting CD4 T Cells in HIV-1 Infected Patients Receiving HAART
authors: T-W Chun, A Fauci, C Lane and others at NIH

As you know, it's been demonstrated by Robert Siliciano that despite reduction of viral load in plasma to undetectable levels for individuals with chronic infection there remain latently infected resting CD4s carrying replication competent virus. This reservoir resides in memory CD4 cells which have a long life and HAART alone does not appear to have much effect on this pool of virus in individuals with chronic infection. This is in contrast to Ho's findings in individuals treated with HAART during acute infection (click here to see Retrovirus report from Zhang on this web page). Chun gave a follow-up report on his study previously reported by Fauci at IDSA in November and the Gallo meeting in September.

The frequency or pool size of resting CD4 cells in blood carrying replication competent HIV in patients receiving IL-2 plus HAART was statistically significantly less than those receiving HAART alone. This is due to the fact that Chun could not find replication competent HIV when using standard coculture assays in 6 out of 14 patients. For the patients receiving HAART alone researchers looked at 10 to 20 million cells, and all 12 patients receiving HAART alone carried infectious HIV in their resting CD4s. For 3 of the 6 patients researchers looked at 330 to 360 million cells (a sensitive assay) and found no evidence of replication competent HIV in this compartment of resting CD4s. In the other 3 patients they looked at just over 100 million cells. In addition using a coculture analysis, they were unable to detect any replication competent virus in the PBMCs of these 3 patients. For a little perspective NIH researchers have suggested that using a different technique such as a sensitive nested PCR assay might result in detecting replication competent virus in this compartment but I don't think this has yet to be firmly established.

Researchers in this study conducted lymph node biopsies on 2 of the 3 patients and were unable to find replication competent virus. They were not able to perform the biopsy on the third person. However, researchers said their findings did not rule out the presence of infectious virus in other reservoirs such as lymph nodes in other parts of the body, bone marrow, the brain, GALT, other lymphocytes. So, they cannot conclude they've eradicated HIV in these patients.

Chun said the mechanisns of the observed effects are unclear and may include purging of the latently infected cells by activation and cell death or enhanced immune-mediated elimination. Chun said the final proof of functional eradication of replication competent virus will be discontinuation of HAART. I believe studies to explore this are underway or in planning.