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Aim: We previously demonstrated that solid drug nanoparticles (SDNs) lopinavir (LPV) dispersed into aqueous media display favorable pharmacokinetics. Methods: The impact of LPV SDNs on the function and phenotype of primary human T cells and macrophages (primary sites of HIV replication) was investigated. Results: LPV significantly increased IL-1β (ninefold higher than untreated cells; p = 0.045) and TNF-α (sixfold higher than untreated cells; p = 0.018) secretion from monocyte-derived macrophages, whereas LPV SDNs did not elicit these responses at comparable drug concentrations. LPV SDNs were demonstrated to be immunologically inert to human T cells and monocyte-derived macrophages. Conclusion: The LPV SDN was demonstrated to exhibit comparable, or favorable behavior compared with an LPV aqueous solution in the employed biocompatibility assessments. [ABSTRACT FROM AUTHOR]