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Effect of HAART and Immune-Based Strategies in HIV-1-Infected Antiretroviral-Naive Adults G. P. RIZZARDI*1, A. CHAPUIS1, G. TAMBUSSI2, P. A. BART1, N. HALKIC1, J. I. MEUWLY1, J. P. CHAVE3, P. MEYLAN1, C. HIRT4, R. MOSS5, H. MCDADE6, W. SPREEN7, A. LAZZARIN2, and G. PANTALEO1. 1CHUV, Lausanne, Switzerland; 2HSR, Milan, Italy; 3Clin. La Source, Lausanne, Switzerland; 4Roche Pharma, Reinach, Switzerland; 5The Immune Response Corp., Carlsbad, CA; 6Glaxo Wellcome, London, UK; and 7Glaxo Wellcome, Res. Triangle Park, NC To evaluate the activity and safety of highly active antiviral therapy (HAART) and immune-based strategies in therapy-naive HIV-1-infected adults with baseline CD4 count <250 cells/µl and plasma viral load (VL) >5000 copies/ml. Abacavir (NRTI), amprenavir, saquinavir s.g.c., and nelfinavir (Pls) are being administered in varying combinations to 33 subjects for 63 weeks. Subjects with VL <400 copies/ml at wk 16 are randomized to add either nihil (gr. A, control), or sc IL-2 (gr. B) (2.5 MU/m2 q 12h for 5 days/6 wks) or a therapeutic vaccine (gr. C) (Remune 10 µg p24/12 wks). Virologic and immunologic measures are assessed in blood and lymph node (LN). VL is measured with a boosted Amplicor assay with a limit of detection of 5 copies/ml. At baseline, the median CD4 count was 570 cells/µl and mean±SD log10 VL was 4.8±0.45 copies/ml. Eleven patients were randomised to gr. A, 7 to gr. B and 10 to gr. C. Overall, VL was highly suppressed over time and no significant differences were seen among gr. A, B and C. Mean changes in VL over baseline were -3.9 at wk 23 and -4.2 at wk 48. Using an intent-to-treat analysis (NC=F), the proportion of patients with <50 copies/ml was 74% at wk 23 (No.=31) and 68% at wk 48 (No.=18). The increase in CD4 count (overall +388 cells/µ1 at wk 48) was significantly higher in gr. B than in both gr. A (p=0.04) and gr. C (p=0.01). LN CD4% significantly increased while LN CD8% decreased over time (p<0.05). The increase in blood and LN CD4 cells was due to both CD45RO+ and CD45RA+ CD4 T cells. HIV-specific lymphocyte proliferative responses (to envelope-depleted HIV and to np24) and DTH responses to HIV antigens were significantly more frequent and sustained in gr. C (80°/a) than in gr. B (30%) and A (20%). Adverse events included diarrhea, nausea, vomiting, and headache. These combination therapies actively suppress HIV-1 replication, and normalize CD4+ T cells in blood and LN. The adjunct of immune-based strategies appears to induce an additional immunologic response. Key Words: HAART, immune-based strategies, lymphnode |
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© 7th
Conference on Retroviruses and Opportunistic Infections, |