Double-negative T cells are increased in HIV-infected patients under antiretroviral therapy

Double-negative T (DNT) cells are a T-cell subset with a CD4-CD8- phenotype. They represent 1% to 5% of circulating lymphocytes, but an increase in this proportion can be found during lymphoproliferative and autoimmune diseases. This increase has also been reported in persons with HIV (PWH). The aim of this work was to better describe the proportion of DNT cell subset in PWH. We retrospectively collected 984 samples from PWH referred for lymphocyte immunophenotyping over a 7.5-year period. Quantification of DNT cells was performed by flow cytometry. DNT cell proportion was calculated by subtracting the CD4+ and CD8+ subsets proportions from the total of T cells. A total of 984 blood samples from PWH were collected. Mean CD4 T-cell count was decreased in such patients while DNT cell frequency was increased with a mean of 6.7%. More than half of the patients had a DNT cell proportion >5%. Patients with DNT cell proportion over 5% exhibited significantly reduced CD3+ and CD4+ T-cell counts, while CD8+ T-cell count was unchanged compared to patients with normal DNT cell rates. Interestingly, DNT cell percentage was negatively correlated with CD4 and CD3 T-cell counts in all included patients. Moreover, the DNT cell proportion was significantly increased in subjects with CD4+ T cells <200/mm3 compared to those with CD4+ T cells >200/mm3. Interestingly, DNT cell proportions were significantly higher in patients with high viral load compared with those presenting undetectable viral load. HIV infection is associated with an increase in DNT cell proportion. This increase is more frequent as the CD4 count is decreased and the viral load is increased. DNT cell subset should not be omitted when interpreting immunophenotyping in PWH as it appears to be associated with disease progression in patients under antiretroviral therapy.