PREDOMINANCE OF DETRIMENTAL HUMORAL IMMUNE-RESPONSES TO HIV-1 IN AIDSPATIENTS WITH CD4 LYMPHOCYTE COUNTS LESS-THAN 400 MM(3)/

The humoral immune response to human immunodeficiency virus type 1 (HI V-1) was studied in 25 AIDS patients with CD4 lymphocyte counts of les s than 400/mm(3). Humoral immune responses against tissue culture adap ted strains of HIV-1, and two limited-passage patient isolates were in vestigated. Total anti-HIV antibody levels were not significantly diff erent between different individuals. Neutralizing titres against HIVLA I and HIVSF2 were 10- to 100-fold higher than against clinical isolate s. The complement-mediated, antibody dependent enhancement of HIV-I in fection titre was high (mean 1:14,000). Antibody-complement mediated c ytotoxicity of both HIVLAI and HIVSF2 was ineffective using human comp lement as a complement source. The antibody-dependent, cell-mediated c ytotoxicity (ADCC) activity varied against the four isolates with tiss ue culture-adapted strains being more susceptible than clinical isolat es. Finally, an ADCC effector cell function, natural killer or NK acti vity, was measured for all 25 patients, and NK activity of patients wa s decreased by nearly 75% compared to uninfected individuals. In summa ry, beneficial humoral immune responses are low in HIV-1 infected indi viduals with CD4 counts of less than 400/mm(3) if the in vitro assay s ystem is constructed to best mimic the in viva situation. These result s suggest that the lack of functional antibody responses to HIV may pl ay an important role in viral pathogenesis.