AUTHOR=Grant-McAuley Wendy , Morgenlander William , Hudelson Sarah E. , Thakar Manjusha , Piwowar-Manning Estelle , Clarke William , Breaud Autumn , Blankson Joel , Wilson Ethan , Ayles Helen , Bock Peter , Moore Ayana , Kosloff Barry , Shanaube Kwame , Meehan Sue-Ann , van Deventer Anneen , Fidler Sarah , Hayes Richard , Ruczinski Ingo , Kammers Kai , Laeyendecker Oliver , Larman H. Benjamin , Eshleman Susan H. TITLE=Comprehensive profiling of pre-infection antibodies identifies HIV targets associated with viremic control and viral load JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1178520 DOI=10.3389/fimmu.2023.1178520 ISSN=1664-3224 ABSTRACT=Background

High HIV viral load (VL) is associated with increased transmission risk and faster disease progression. HIV controllers achieve viral suppression without antiretroviral (ARV) treatment. We evaluated viremic control in a community-randomized trial with >48,000 participants.

Methods

A massively multiplexed antibody profiling system, VirScan, was used to quantify pre- and post-infection antibody reactivity to HIV peptides in 664 samples from 429 participants (13 controllers, 135 viremic non-controllers, 64 other non-controllers, 217 uninfected persons). Controllers had VLs <2,000 copies/mL with no ARV drugs detected at the first HIV-positive visit and one year later. Viremic non-controllers had VLs 2,000 copies/mL with no ARV drugs detected at the first HIV-positive visit. Other non-controllers had either ARV drugs detected at the first HIV-positive visit (n=47) or VLs <2,000 copies/mL with no ARV drugs detected at only one HIV-positive visit (n=17).

Results

We identified pre-infection HIV antibody reactivities that correlated with post-infection VL. Pre-infection reactivity to an epitope in the HR2 domain of gp41 was associated with controller status and lower VL. Pre-infection reactivity to an epitope in the C2 domain of gp120 was associated with non-controller status and higher VL. Different patterns of antibody reactivity were observed over time for these two epitopes.

Conclusion

These studies suggest that pre-infection HIV antibodies are associated with controller status and modulation of HIV VL. These findings may inform research on antibody-based interventions for HIV treatment.