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C. Pastori1, C. Barassi1, F. Lillo1, P. Marraccini2, C. De Santis1, D. Ciuffreda3, B. Capiluppi1, A. Lazzarin1, G. Tambussi1, and L. Lopalco1*
1San Raffaele Scientific Inst., Milan, Italy; 2UOOML-CEMOC, Milan, Italy; and 3CHUV, Lausanne, Switzerland
Background: HIV-1 infection is associated with a strong antibody response directed to envelope protein. However, neutralizing antibodies develop slowly and after many months of infection. It is unclear whether the highly active antiretroviral therapy (HAART) may affect immunological humoral function in primary or chronic HIV-1-infected patients. The effects of HAART on humoral immunity during a 24-month follow-up of 20 primary HIV-infected patients were investigated.
Methods: The patients were divided in 3 groups: (a) 5 patients treated with Zidovudine (ZVD); (b) 8 patients on a triple combination of ZVD + lamivudine (3TC) + saquinavir (SQV); and (c) 7 patients on a 4-drug combination of ZVD + 3TC + SQV + ritonavir (RTV).
Results: The early introduction of HAART greatly reduces plasma viremia levels and restores the number of CD4 cells. A significant correlation was found between anti-HIV neutralizing activity and the 4-drug, but not the 3-drug combination. The infectivity reduction was directed against viruses of different clades and associated with immunoglobulin fractions. The neutralizing antibodies appeared after 2 weeks of treatment and remained stable throughout the 24 months of follow up. Neutralizing antibodies are directed to the external portion of gp41 protein.
Conclusions: These findings may be useful in developing new strategies designed to achieve a long-term control of the infection.
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