Effect of interleukin-2 on the pool of latently infected, resting CD4+ T cells in HIV-1-infected patients receiving highly active anti-retroviral therapy

Abstract

The size of the pool of resting CD4+ T cells containing replication-competent HIV in the blood of patients receiving intermittent interleukin (IL)-2 plus highly active anti-retroviral therapy (HAART) was significantly lower than that of patients receiving HAART alone. Virus could not be isolated from the peripheral blood CD4+ T cells in three patients receiving IL-2 plus HAART, despite the fact that large numbers of resting CD4+ T cells were cultured. Lymph node biopsies were done in two of these three patients and virus could not be isolated. These results indicate that the intermittent administration of IL-2 with continuous HAART may lead to a substantial reduction in the pool of resting CD4+ T cells that contain replication-competent HIV.

Macrophage Colony-Stimulating Factor Antagonists Inhibit Replication of HIV-1 in Human Macrophages

“…Clinical trials for HIV-infected patients using highly active antiretroviral therapy (HAART) reported a prolonged absence of plasma viremia, followed by a rapid viral rebound upon discontinuation of therapy, suggesting a failure of this approach to eradicate HIV in existing viral reservoirs (35). Recent studies have been conducted using the cytokine, IL-2, in combination with HAART to activate HIV-1-infected T cell reservoirs and render them susceptible to therapy (36). However, other potential reservoirs exist, including the macrophage, which would not be affected by this approach.…”

Prostratin Antagonizes HIV Latency by Activating NF-κB

“…Efforts to eliminate this pool of latently infected cells with interleukin-2 and OKT3 antibodies yielded disappointing results (8,9). For this lofty goal to be reached, more efficient and less toxic antagonists of HIV latency must be identified, and the variegated nature of the response must be successfully dealt with.…”

“…However, clinical efforts aimed at eliminating the pool of latently infected cells by induction with IL-2 or anti-CD3 OKT3 antibodies have yielded discouraging results (8,9).…”

Biochemical mechanisms of HIV induced T cell apoptosis

“…A recent report showed that three patients treated with continuous HAART and intermittent IL-2 had significantly fewer resting CD4 + T cells harboring replication-competent HIV RNA. 103 IL-2 therapy with anti-retroviral drugs not only activates the immune system and, possibly, HIV from latently infected cells, but also, interestingly, decreases the plasma viral load in some patients. 104 These studies are encouraging, although more patients and long term monitoring are required before definitive conclusions can be drawn.…”