Hypergammaglobulinemia in treated and untreated people with HIV

BACKGROUND: B cell abnormalities are an early feature of human immunodeficiency virus-1 (HIV) infection, leading to hypergammaglobulinemia. OBJECTIVE(S): The aim of this study was to evaluate serum levels of immunoglobulin G (IgG) as well as the inflammatory biomarkers neopterin, β2-microglobulin and albumin in a large cohort of untreated as well as virologically suppressed people with HIV (PWH) on antiretroviral therapy (ART). METHODS: We conducted a cross-sectional analysis of blood samples from untreated PWH and virologically suppressed participants on ART. Of 750 collected blood samples, 267 were from ART-suppressed participants and 483 from untreated participants. Levels of IgG, HIV-RNA, CD4+ T cells, β2-microglobulin, neopterin and albumin were analyzed with regard to age, sex and stage of HIV infection. RESULTS: Hypergammaglobulinemia was present in all subgroups of untreated PWH except in those with primary HIV infection. Participants with a CD4+ T cell count between 50 and 349 cells/µL exhibited the highest IgG concentrations. Elevated IgG concentrations prevailed in 24% of participants on ART. Serum neopterin and β2-microglobulin levels were significantly elevated in untreated PWH. They decreased in participants on ART, but remained abnormally elevated in approximately half of those. CONCLUSION: Although IgG levels were normalized in a majority of participants on ART, hypergammaglobulinemia prevailed in about a quarter of cases, indicating a remaining B cell hyperactivity despite viral suppression. The finding of elevated levels of inflammatory biomarkers despite ART suppression is suggestive of residual inflammatory activity and parallels the finding of persisting hypergammaglobulinemia.