The majority of HIV type 1 DNA in circulating CD4+ T lymphocytes is present in non-gut-homing resting memory CD4+ T cells.

Memory CD4(+) T lymphocytes in peripheral blood that express integrins α4ß7 preferentially recirculate through gut-associated lymphoid tissue (GALT), a proposed site of significant HIV-1 replication. Tregs and activated CD4(+) T cells in GALT could also be particularly susceptible to infection. We therefore hypothesized that infection of these subsets of memory CD4(+) T cells may contribute disproportionately to the HIV-1 reservoir. A cross-sectional study of CD4(+) T cell subsets of memory CD45RO(+) cells in peripheral blood mononuclear cells (PBMCs) was conducted using leukapheresis from eight subjects with untreated chronic HIV-1 infection. Real-time polymerase chain reaction (PCR) was used to quantify total and integrated HIV-1 DNA levels from memory CD4(+) T cells sorted into integrin β7(+) vs. β7(-), CD25(+)CD127(low) Treg vs. CD127(high), and activated CD38(+) vs. CD38(-). More than 80% of total HIV-1 DNA was found to reside in the integrin β7-negative non-gut-homing subset of CD45RO(+) memory CD4(+) T cells. Less than 10% was found in highly purified Tregs or CD38(+) activated memory cells. Similarly, integrated HIV-1 DNA copies were found to be more abundant in resting non-gut-homing memory CD4(+) T cells (76%) than in their activated counterparts (23%). Our investigations showed that the majority of both total and integrated HIV-1 DNA was found within non-gut-homing resting CD4(+) T cells.