Multiple HIV-1 specific IgG3 responses decline during acute HIV-1: implications for detection of incident HIV Infection

Abstract

OBJECTIVE:: Different HIV-1 antigen specificities appear in sequence post HIV-1 transmission and the IgG subclass response to HIV antigens are distinct from each other. The initial predominant IgG subclass response to HIV-1 infection is comprised of IgG1 and IgG3 antibodies with a noted decline in some IgG3 antibodies during acute HIV-1 infection. Thus, we postulate that multiple antigen specific IgG3 responses may serve as surrogates for the relative time since HIV-1 acquisition. DESIGN:: We determined the magnitude, peak, and half-life of HIV-1 antigen specific IgG1 and IgG3 antibodies in 41 HIV-1 infected subjects followed longitudinally from acute infection during the first appearance of HIV-1 specific antibodies through approximately six months post infection. METHODS:: We used quantitative HIV-1 binding antibody multiplex assays and exponential decay models to calculate concentrations of IgG1 and IgG3 antibodies to eight different HIV-1 proteins including gp140 Env, gp120 Env, gp41 Env, p66 Reverse Transcriptase (RT), p31 Integrase, Tat, Nef, and p55 Gag proteins during acute/recent HIV-1 infection. RESULTS:: Among HIV-1 specific IgG3 responses, antigp41 IgG3 antibodies were the first to appear. We found that antigp41 Env IgG3 and antip66 RT IgG3 antibodies, in addition to anti-Gag IgG3 antibodies, each consistently and measurably declined after acute infection, in contrast to the persistent antigen specific IgG1 responses. CONCLUSIONS:: The detailed measurements of the decline in multiple HIV-specific IgG3 responses simultaneous with persistent IgG1 responses during acute and recent HIV-1 infection could serve as markers for detection of incident HIV infection