Antiretroviral therapy does not correct the dysregulations of plasma virome and cytokines induced by HIV-1

HIV-1 infection leads to an expansion of plasma anelloviruses and dysregulation of inflammation. However, the effects of antiretroviral therapy (ART) on dynamics of plasma virome and cytokine profile are not well-understood. To characterize the dynamics of plasma virome and 27 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 found for other plasma commensal viruses. Increased abundance and prevalence of HPgV-1 were further confirmed by RT-qPCR assay in a larger cohort of 114. Notably, most cytokines dysregulated were not fully restored by ART, with 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 corrections with several anti-inflammatory and Th1 cytokines. These results indicate that ART does not significantly correct the virome and cytokine dysregulations associated with HIV-1 infection.