Long lived T cells for treating HIV infection

A method of generating an enriched population of long-lived CD4 T cells that are devoid of a functional CCR5 and/or CXCR4 HIV co-receptor;

• the method comprising:
• isolating CD4 T cells from a biological sample of a subject;
• separating and/or enriching isolated CD4 T cells into cells having a CD45RAintCD45ROint phenotype and an increased expression of TCF7 compared to the isolated CD4 T cells prior to separation and/or enrichment, wherein enriching includes culturing the isolated CD4 T cells in the presence of IL-7 and IL-15 effective to promote expansion and/or formation of an enriched population of CD4 T cells having the CD45RAintCD45ROint phenotype, wherein the concentration of IL-7 and IL-15 is less than 10 ng/ml, and wherein at least 50% of the separated and/or enriched population of CD4 T cells have a CD45RAintCD45ROintCD95+CD127+CD27+ phenotype;
• and
• modifying the CD4 T cells such that the CD4 T cells are devoid of a functional CCR5 and/or CXCR4 HIV co-receptor before separating and/or enriching the isolated CD4 T cells into cells having the CD45RAintCD45ROint phenotype and/or modifying the separated and/or enriched CD4 T cells having the CD45RAintCD45ROint phenotype such that the CD4 T cells having the CD45RAintCD45ROint phenotype are devoid of a functional CCR5 and/or CXCR4 HIV co-receptor.