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 after HIV-1 transmission and the immunoglobulin G (IgG) subclass responses to HIV antigens are distinct from each other. The initial predominant IgG subclass response to HIV-1 infection consists 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 individuals followed longitudinally from acute infection during the first appearance of HIV-1-specific antibodies through approximately 6 months after infection.

Methods: We used quantitative HIV-1-binding antibody multiplex assays and exponential decay models to estimate concentrations of IgG1 and IgG3 antibodies to eight different HIV-1 proteins including gp140 Env, gp120 Env, gp41 Env, p66 reverse transcriptase, p31 Integrase, Tat, Nef, and p55 Gag proteins during acute/recent HIV-1 infection.

Results: Among HIV-1-specific IgG3 responses, anti-gp41 IgG3 antibodies were the first to appear. We found that anti-gp41 Env IgG3 and anti-p66 reverse transcriptase 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.

Conclusion: 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.

Fig. 1

HIV-specific IgG3 antibody responses peak sequentially during acute HIV-1 infection. Mean concentrations of HIV-specific IgG3 are shown in a longitudinal model in which responses were aligned to study enrollment and adjusted for time after HIV-1 acquisition according to the classification by Fiebig et al. [22].

Fig. 2

Levels of HIV-1-specific IgG1 remain stable, whereas HIV-1-specific IgG3 declines over time during acute HIV-1 infection. Declining HIV-1-specific IgG3 antibody responses were aligned according to the peak of each response, modeled over time, and response half-life was estimated using the exponential decay model. Half-life in days (95% confidence interval) and N (number of participants with at least one positive time point after peak) are depicted in each panel (a). HIV-1-specific IgG1 antibody levels did not decline and, therefore, were not fit to the exponential decay model. For this reason, IgG1 antibody responses were aligned to enrollment into the study (b).