Expansion of pathogens and restoration of human skin microbiome in CD4 T-cell lymphopenia

The microbiome and host immune system maintain a dynamic homeostatic equilibrium at the skin interface. Prior studies have shown that the skin microbiome is profoundly altered in immunodeficient conditions. Patients with idiopathic CD4 lymphopenia, a rare clinical syndrome with an obscure cause, and people living with HIV are 2 etiologically distinct groups of individuals with CD4 T-cell lymphopenia. We conducted shotgun metagenomic sequencing, metagenome assembly, and read-based mapping to examine the multi-kingdom taxonomic diversity of skin microbiomes in patients with idiopathic CD4 lymphopenia and people living with HIV who were followed longitudinally before and after initiation of antiretroviral therapy. Compared with healthy individuals, the skin microbiomes of patients with idiopathic CD4 lymphopenia and antiretroviral therapy-naïve people living with HIV showed greater inter-individual variation and higher relative abundances of eukaryotic viruses. Both patient groups carried pathogenic microbes, including high-oncogenic-risk human papillomaviruses and dermatophytes such as Trichophyton rubrum, which were rarely seen in healthy controls. In people living with HIV, high-oncogenic-risk human papillomaviruses persisted after 2 months of antiretroviral therapy but were mostly cleared after 14 months. The loss of peripheral blood CD4 T-cells was associated with shifts in the skin microbiome and a relative expansion of pathogenic microbes. Investigating microbiome dynamics during immunodeficiency and subsequent immune reconstitution provides additional insights into host-microbial interactions.