Strong correlation between the complement-mediated antibody-dependent enhancement of HIV-1 infection and plasma viral load

Objective: We have previously demonstrated that complement-mediated antibod y-dependent enhancement (C-ADE) of HIV-1 infection correlates with accelera ted immunosuppression and disease progression in HIV-1-infected individuals . In the present work the relationship between C-ADE and plasma HIV-1 RNA c oncentrations was studied to determine the effect of C-ADE on viral replica tion. Methods: Three studies were performed: (a) C-ADE and HIV-1 RNA concentratio ns were determined in the serum and plasma aliquots taken at the same time from 98 HIV patients, mostly in the advanced stage of the disease; (b) the above two parameters as well as HIV enzyme-linked immunosorbent assay (ELIS A)-reactive antibodies (Abbott HIV 1/2 test), and p24 antigen levels (Abbot t antigen test; Abbott, Delkenheim, Germany) were determined in four seroco nversion panels purchased from the Boston Biomedica firm; (c) changes of HI V-1 RNA concentration and C-ADE during a 17 month follow-up period were det ermined in 18 HIV-infected patients. C-ADE was measured by the method previ ously established in our laboratories. The results were expressed by an enh ancement/neutralization index (E/NI). HIV-1 RNA levels were determined with the Amplicor monitor kit (Roche, Baser, Switzerland), and in some experime nts with the nucleic acid sequence based amplification (Organon Teknika, Tu rnhout, Belgium) kits. Results: (a) We found a highly significant (P < 0.0001) positive correlatio n between E/NI values reflecting the extent of HIV-1 infection enhancement and plasma HIV-1 RNA levels. Both E/NI and HIV-1 RNA levels negatively corr elated to the CD4 cell counts. (b) C-ADE was first detected just before, or concomitantly with, seroconversion in 4/4 seroconversion panels. (c) Both E/NI values and HIV-1 RNA levels significantly (P < 0.001) increased during a 17 month observation period in 18 HIV-infected patients. Conclusion: We found strong association between the extent of the complemen t-mediated antibody-dependent enhancement of HIV-1 infection and the plasma viral load in HIV patients. On the basis of these findings, C-ADE correlat es with HIV replication in vivo, and potentially contributes to the progres sion of HIV disease. (C) 1999 Lippincott Williams & Wilkins.