AEGiS-14IAC: Intermittent cycles of IL-2 increase CD4+ T cell counts but do not enhance antibody responses to immunization: results of A5046s.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Intermittent cycles of IL-2 increase CD4+ T cell counts but do not enhance antibody responses to immunization: results of A5046s.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. ThOrA1481)

Valdez H, Lederman MM, Pollard RB, Sahner D, Sevin A, Chan E, Moss R, Estep S, Fox L, Namkung A, Mitsuyasu R, Landay A, Fahey JL
Case Western Reserve Center for AIDS Research, Cleveland, United States

BACKGROUND: IL-2 increases the numbers of CD4+ cells in patients with HIV infection. We wished to ascertain whether increasing CD4+ cell numbers would improve antibody responses to immunization.

METHODS: ACTG 328 compared CD4 changes in patients treated with HAART ± IL-2; to qualify patients had to have CD4+ counts < 350. 38 patients with viral loads (VL) <2000 c/mL after at least 60 weeks on ACTG 328 received Remune (inactivated, gp-120 depleted HIV: 3 times 2 months apart) and Tetanus Toxoid (twice 2 months apart). Hepatitis A (HA) and/or B (HB) unexposed patients received HA (twice 2 months apart) and/or HB vaccines (3 times 2 months apart). IL-2 administration and immunizations were separated by 4 weeks. IL-2 dose: 4.5 MIU SQ BID for 5 days every 8 weeks.

RESULTS: Patients were on HAART for 98 weeks prior to enrolling in A5046s. Patients in the IL-2 group (25 of 38) received 10 cycles prior to immunization. Pre-HAART CD4+ (221 vs. 242) and CD8+ (458 vs. 446) counts were similar; but at immunization the IL-2 group had higher CD4+ (865 vs. 444, p= 0.02) and CD8+ (969 vs. 718, p< 0.03) counts. Pre-HAART VL was higher in the IL-2 group (4.6 vs. 3.7 log₁₀, p=0.06), but was similar at immunization. At week 24, 36% of patients in each group developed a 4-fold rise in p24 antibodies. Also, 30% of HAART+IL-2 patients and 40% of HAART alone recipients developed a 4-fold rise in tetanus antibodies. Compared to HAART + IL-2 recipients, there was a trend for a greater proportion of HAART alone recipients to develop antibody responses after HA immunization (88% vs 36%, p=0.06 at week 24) while a similar proportion of patients in each group responded to HB (50% vs. 13%, p=0.25 at week 24).

CONCLUSIONS: While intermittent high dose IL-2 increases the number of circulating CD4+ cells, these additional CD4+ cells do not confer an enhanced antibody response to immunization.

Keywords: AEGIS, CD4 Lymphocyte Count, Interleukin-2, T-Lymphocytes, Immunization, Antiretroviral Therapy, Highly Active, Antibody Formation, Vaccination, CD4-Positive T-Lymphocytes, HIV Infections, Viral Load, AIDS Vaccines, Tetanus Toxoid, Antigens, CD4, HIV Seropositivity, Antigens, CD8, remune, Human, immunology

020707
ThOrA1481