Blood T cell receptor repertoire sequencing in HIV-negative healthy volunteers and people living with HIV on effective, long-term anti-retroviral therapy

Immune activation in people living with HIV on anti-retroviral therapy is associated with increased risk of morbidity and mortality, but the underlying mechanisms are poorly understood. Untreated HIV infection leads to a profound reduction in the diversity of T cell clones and oligoclonal T cell expansion reflected by T cell receptor sequence analysis, resulting in skewed and highly idiosyncratic repertoires. To identify whether abnormalities in the clonal T cell repertoire persist despite long-term anti-retroviral therapy, we used high-throughput T cell receptor sequencing of whole blood samples from 26 people living with HIV on long-term anti-retroviral therapy and 12 HIV-negative healthy controls. All participants were Caucasian male adults recruited from London, UK. People living with HIV were on anti-retroviral therapy for a median of 8.5 years (interquartile range 3-16 years). They had undetectable plasma HIV viral load (<40 copies/ml) and median circulating CD4 counts of 703 cells/microliter (interquartile range 491-841 cells/microliter).