Background: Recent literature describes a minor subset of monocytes characterised by lower CD14 (LPS receptor) and higher CD16 (Fcg receptor III) surface expression than the major monocyte population. Our preliminary data support previous studies that the CD14^lo/CD16^hi subset is significantly expanded in HIV-infected individuals and that these cells express higher CCR5 than CD14^hi monocytes.

Methods: We and others have shown infectious HIV has been recovered from the peripheral blood of HIV-infected individuals on HAART with undetectable viral load. Our recent data suggest it is the CD14^lo/CD16^hi monocytes that selectively harbour HIV in these infected individuals. CD14^lo/CD16^hi and CD14^hi/CD16^- monocytes were enriched from peripheral blood collected from 6 HIV⁺ patients (pts) using magnetic bead technology. A highly sensitive nested PCR for HIV-specific gag DNA showed monocytes in 5 of the 6 pts harboured HIV; HIV DNA was only detected in the CD14^lo/CD16^hi monocytes and not in the CD14^hi/CD16^- monocytes. Our data also suggest CD14^lo/CD16^hi monocytes may be more permissive to HIV infection in vitro than the majority of monocytes. Monocyte subsets were isolated from HIV-seronegative buffy coats by high-speed flow-cytometric sorting. Cells from each subset were pulsed for 2 hrs with DNase-treated HIV-1_Ba-L at an MOI of 0.1–1 infectious particles per cell. Excess virus was washed from the cell surface and cells were cultured for a further 48 hrs to allow reverse transcription. Significantly higher levels of HIV-specific DNA were in the CD14^lo/CD16^hi monocytes as detected by real-time PCR.

Conclusions: We hypothesise that HIV-1 replication persists in tissue reservoirs in HAART patients with undetectable viral load, and that these reservoirs are continually patrolled by a minor population of monocytes which has heightened susceptibility to HIV infection (possibly due to increased CCR5 expression).