Short-term antiretroviral therapy may not correct the dysregulations of plasma virome and cytokines induced by HIV-1 infection.

An expansion of plasma anelloviruses and dysregulation of inflammation was associated with HIV-1 infection. However, how antiretroviral therapy (ART) affects the dynamics of plasma virome and cytokine profile remains largely unknown. To characterize the dynamics of plasma virome and cytokines in HIV-1-infected individuals before and during the first year of ART, a cohort of 26 HIV-1-infected individuals and 19 healthy controls was recruited. Blood samples were collected and subjected to metagenomic analysis and the measurement of 27 cytokines. Metagenomic analysis revealed an increased abundance and prevalence of human pegivirus type 1 (HPgV-1) and a slightly decreased diversity and abundance of anellovirus in plasma of HIV-1-infected individuals after ART. No obvious impact was observed on other plasma commensal viruses. Increased abundance and prevalence of HPgV-1 were further confirmed by RT-qPCR assay in a larger cohort of 114 HIV-1-infected individuals. Notably, most dysregulated cytokines were not fully restored by ART, with extremely abnormal levels of IL-10, GM-CSF, VEGF, and eotaxin, and a significantly increased level of plasma I-FABP. Anelloviruses showed significantly negative correlations with other commensal viruses except HPgV-1 but had positive correlations with several anti-inflammatory and Th1 cytokines. These results suggest that short-term ART may not significantly correct the virome and cytokine dysregulations induced by HIV-1 infection. The results highlight a need for further investigation into the long-term effects of ART on virome and cytokine profiles in HIV-1-infected individuals.