HIV-1 induced in the setting of IL-2 therapy is transient and not derived from PBMC proviral reservoirs

Intermittent 5-day administration of rIL-2 leads to sustained increases in CD4 T cell counts in patients with HIV infection. It can also lead to a transient increase in plasma levels of HIV-1 RNA. Despite this transient increase in levels of HIV-1, the long-term consequences of IL-2 therapy are a decrease in plasma HIV-1 RNA levels. More recent data have also suggested the possibility that IL-2 therapy may lead to decreases in the HIV-1 reservoir. To better understand the effects of intermittent IL-2 on HIV-1 expression, a detailed kinetic and quasi-species analysis of HIV-1 expression was carried out in the context of intermittent IL-2 therapy. Plasma HIV-1 RNA levels were measured daily for 10 days in 11 patients. 6/11 patients showed at least a 0.5 log increase in plasma HIV-1 RNA levels during at least 1 cycle of IL-2. Among the other 5 patients, 3 showed a > 0.5 log decrease in at least 1 cycle and 2 showed no change. HIV quasi-species analyses were carried out on PBMC proviral DNA and plasma RNA in 8 patients at days 0, 5 or 6, and 28 of an IL-2 cycle. In 6 of the patients, the viruses seen at day 5 or 6 were indistinguishable from the viral quasi-species present at day 0. In the other 2 patients the day 6 virus represented unique specific clusters. There were no instances in which the day 5 or 6 virus was clearly derived from PBMC proviral DNA sequences. Thus, the expression of HIV-1 induced by IL-2 is transient, is only seen in about 50% of patients and most likely represents amplification of pre-existing replicating viral species rather than activation of silent reservoirs of proviral DNA in PBMC.

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