Neutralizing and enhancing antibodies measured in complement-restored serum samples from HIV-1-infected individuals correlate with immunosuppression and disease

To study the association between the progression of HIV disease and HIV neutralization and enhancement measured in the presence of human complement. Two studies were performed: (1) longitudinal measurement of the complement-dependent enhancing antibodies in parallel with T-cell subset determination in 55 serum samples from seven HIV-infected patients, and (2) determination of the titres of neutralizing and enhancing antibodies in stored samples of 21 HIV-asymptomatic patients obtained between 1986 and 1987 and follow-up of the patients until October 1992. HIV-1 [human T-lymphotropic virus (HTLV)IIIB strain, 100 median tissue culture infective dose (TCID50)] was incubated with twofold dilutions of sera in the presence of human complement (final dilution, 1:4) and added to MT-4 cells. HIV growth was monitored daily for 5 days using the reclustering inhibition and p24 immunofluorescence assays. A significant negative correlation between the titres of enhancing antibodies and CD4+ cell count was found in longitudinal measurements. In the prospective studies, marked differences were observed between patients with undetectable, low, or high titres of enhancing antibodies in the clinical course of HIV disease: CD4+ cell counts and percentages decreased more rapidly in the high titre group within 3 years. After 5 years, AIDS developed in five out of six patients in the high titre group but only in five out of 15 of the low titre group (P < 0.05). A similar difference was observed between patients with and without neutralizing antibodies. Measurement of HIV neutralization and enhancement in complement-containing serum samples using a complement receptor carrying target may provide data of clinical relevance. Neutralization appears to be associated with a favourable prognosis whereas high titre enhancing antibodies predict rapid progression of HIV disease.