Abstract

Interleukin-16 (IL-16) and the beta-chemokines (RANTES, monocyte chemotactic protein-1 (MCP-1), macrophage inhibitory protein (MIP)-1alpha and (MIP)-1beta) are soluble in vitro suppressors of macrophage tropic HIV-1 strains. The reduction of HIV-1 RNA plasma levels in late-stage patients receiving protease inhibitors has been associated with increased concentrations of MIP-1alpha, MIP-1beta, RANTES and IL-16 and a decrease in levels of MCP-1. We determined plasma levels of MCP-1, MIP-1alpha, MIP-1beta, RANTES and IL-16 during the first 16 weeks of highly active antiretroviral therapy (HAART) in chronic HIV-1-infected patients. Patients were administered one of two therapeutic regimens based on either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). No differences were seen in the levels of RANTES and IL-16 over the first 16 weeks of HAART in either treatment group. MCP-1 decreased significantly in the PI-treated group over the first 16 weeks of HAART (P = 0.0003). A significant increase was observed in the levels of MIP-1alpha and MIP-1beta in the NNRTI cohort (P = 0.0010 and P = 0.0012, respectively). A significant decrease in levels of MIP-1alpha and MIP-1beta (P = 0.0015 and P = 0.0299, respectively) was observed over the 16 weeks in the PI cohort. A significant difference was seen when the levels of MIP-1alpha and MIP-1beta were compared between the NNRTI and the PI cohorts at week 16 (P = 0.04 and P = 0.05, respectively). Evaluation of CCR5 expression ex vivo revealed no difference between the two treatment groups. Patients were genotyped for CCR5 Delta32 and the incidence of heterozygosity was lower than in the HIV-1 seronegative controls (3% compared to 19%).