ANTIBODY-RESPONSES TO HIV-1 ENVELOPE AND GAG EPITOPES IN HIV-1 SEROCONVERTERS WITH RAPID VERSUS SLOW DISEASE PROGRESSION

We studied the relationship between the rate of disease progression af ter HIV-1 seroconversion and the level of IgG antibody response to HIV -1 envelope and core epitopes. This was done by comparing a group of f ast-progressing individuals and a group of slow-progressing individual s for serum IgG titers to peptides from the gp120-V3 neutralization do main, to a peptide from the immunodominant gp41 epitope (residues 590 to 607), and to recombinant gp120 and p24. The two groups displayed a large overlap in titers to the envelope epitopes, which precluded thei r differentiation at most time points after seroconversion. Low respon siveness to envelope antigens was not only found in a few fast-progres sors but also in one individual who remained asymptomatic for at least 92 months after seroconversion. The only significant differences betw een the groups were found in the first months after seroconversion whe n the responses to the V3 domain and the gp41 epitope were more vigoro us in the group of fast-progressors. Furthermore, on evaluating ratios of anti-V3 antibody titers to anti-gp120 antibody titers we found no indication that fast disease progression was associated with a restric tion in antibody response to the V3 epitope. We did confirm the findin g that fast disease progression is associated with low levels of p24-d irected antibodies, both early after seroconversion and at later stage s. These data demonstrate that levels of IgG antibodies to envelope ep itopes are poor predictors of rapid disease progression and suggest th at the role of V3-directed neutralizing antibodies in preventing subve rsion of the immune system is not decisive in natural HIV-1 infection. (C) 1994 Academic Press, Inc.