Subcutaneous Administration of Interleukin‐2 in Human Immunodeficiency Virus Type 1—Infected Persons

Abstract

The safety and efficacy were assessed of 5-day cycles of subcutaneous (sc) interleukin-2 (IL-2) every 8 weeks in human immunodeficiency virus type 1-infected outpatients with >200 CD4 cells/mm3. Immunologic, virologic, and toxicity parameters were measured in 18 patients receiving standard antiretrovirals plus 5-day courses of sc IL-2 (3-18 MIU/day) every 2 months. Systemic toxicities established the maximally tolerated dose (MTD) of IL-2 as 15 MIU/day. CD4 cell responses appeared to correlate directly with baseline CD4 cell counts, with several patients experiencing a dramatic rise after 3 cycles. Virus load increased only transiently in the peri-injection period. It was concluded that serial cycles of outpatient sc IL-2 can be administered safely, with an MTD of 15 MIU/day. Patients with higher baseline counts appear to have a greater CD4 cell response to sc IL-2 therapy.

A Randomised Trial of Subcutaneous Intermittent Interleukin-2 without Antiretroviral Therapy in HIV-Infected Patients: The UK–Vanguard Study

“…Increases in CD4 T lymphocyte count arising from the use of intermittent IL-2 in combination with antiretroviral therapy have been demonstrated consistently in a number of randomised clinical trials [ 13 – 21 ]. The use of recombinant IL-2 has been associated with transient rises of plasma HIV RNA levels in some patients [ 13 – 14 ]. However, no significant persistent increase in HIV RNA has been observed in IL-2 recipients when compared to controls treated with combination antiretroviral therapy [ 13 – 21 ].…”

CD8+ T‐cell effector function and transcriptional regulation during HIV pathogenesis

“…IL-2 production by CD8 + T cells is correlated with proliferation of CD8 + cells independent of CD4 + T-cell IL-2 production (36), and both IL-2 production and proliferation are preserved in nonprogressive HIV infection (39, 40). However, IL-2-induced activation and proliferation of CD4 + T cells may also increase the availability of target cells for infection as well as increase viral replication by infected cells (41). …”

Cytokine production and dysregulation in HIV pathogenesis: Lessons for development of therapeutics and vaccines

“…HIV viremia also correlates with the inability to develop functional HIV-specific CD4 + T cells that can produce IL-2 [80]. However, IL-2 can induce HIV replication in T cells, and it has been shown that administration of IL-2 in vivo can cause ‘blips’ in plasma viral load [81]. IL-2 also induces CD8 + T cell-mediated HIV suppression, which likely counterbalances the increase in HIV replication [82].…”