Effects of IL-2 therapy in asymptomatic HIV-infected individuals on proliferative responses to mitogens, recall antigens and HIV-related antigens

Abstract

The effects of IL-2 therapy on lymphoproliferative responses to mitogens, recall antigens and HIV epitopes were studied in asymptomatic HIV-infected patients enrolled in a phase II study of intermittent continuous intravenous (Ci.v.) IL-2 and subcutaneous infusions of polyethylene glycol-modified (PEG) IL-2. Sixteen consecutive patients randomized to receive Ci.v. IL-2 (n = 5), PEG IL-2 (n = 7) or anti-viral therapy alone (n = 4) were studied. All patients were vaccinated with tetanus toxoid (TT) before receiving therapy. Proliferative responses to phytohaemagglutinin (PHA), soluble anti-CD3, TT, streptokinase/streptodornase (SK/SD) and 11 previously described HIV-specific T-helper epitopes from gag and env were studied at weeks 0, 16, 30 and 48. Median CD4+ lymphocyte increases of 272 and 255CD4+ cells/microl were observed in the Ci.v. IL-2 and PEG IL-2 groups at week 48, while decreasing by 104 cells/microl in the anti-retroviral therapy alone group. At each time point proliferative responses to PHA, anti-CD3, TT and SK/SD were not different between treatment arms. Similarly, no differences in responses to HIV epitopes were found between the groups and no new responses to HIV epitopes were detected. IL-2 therapy results in a significant increase in peripheral blood CD4+ lymphocyte count, but this increase is not associated with quantifiable improvements in lymphoproliferative responses to mitogens, recall or HIV antigens.

Fig. 1

Responses of individual therapy groups to phytohaemagglutinin (PHA). A, B, C shows responses of groups A, B, C for each patient grouped according to their respective treatment allocation (A, anti-retroviral therapy; B, intermittent continuous intravenous (CIV) IL-2; C, polyethylene glycol (PEG) IL-2) at weeks 0, 30 and 52. Median values for A, 46 412, 33 627, 76 869 ct/min for 0, 30 and 52 weeks, respectively; B, 49 267, 36 319, 32 650* ct/min; C 56 491, 42 775, 34 509 ct/min. Each median shown as cross bar. Responses significantly different from HIV⁻ control group: *P < 0.05. Responses of groups B and C were not significantly different from A at any time point.

Fig. 2

Proliferative responses to tetanus toxoid (TT) following IL-2 therapy. Data presented as for previous figure. Subjects receiving booster vaccinations are excluded from this analysis. Median values for TT response: A, 62 825, 10 952, 33 283 ct/min; B, 112 833, 72 205, 81 356 ct/min; C, 76 505, 95 384, 131 832 ct/min at weeks 0, 30 and 52, respectively. No response differed significantly from the HIV⁻ control group at any time point.

Fig. 3

Responses to HIV-derived peptides. Responses in each treatment group to HIV-derived peptides at week 0 and at week 52 in terms of: (a) total HIV-specific response; (b) number of positive responses (n).