Change in circulating levels of the chemokines macrophage inflammatory proteins 1 alpha and 11 beta, RANTES, monocyte chemotactic protein-1 and interleukin-16 following treatment of severely immunodeficient HIV-infected individuals with indinavir.

OBJECTIVE

To evaluate the in vivo relationship between HIV replication and circulating levels of the chemokines macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, RANTES (acronym for Regulated upon Activation, Normal T-cell Expressed and presumably Secreted), interleukin (IL)-16 and monocyte chemotactic protein (MCP)-1, which have recently been characterized as factors capable of regulating in vitro HIV replication.

DESIGN AND METHODS

We have compared changes in plasma HIV-RNA levels and circulating levels of MIP-1 alpha, MIP-1 beta, RANTES, IL-16 and MCP-1 in 20 severely immunodeficient HIV-infected individuals (CD4+ T cells = 14 +/- 3 cells x 10(6)/l; plasma HIV RNA = 4.45 +/- 0.27 log 10 copies/ml) undergoing treatment with the HIV protease inhibitor indinavir that added to pre-existing nucleoside-based therapy. At weeks 0, 2, 6 and 12, viral load was quantified using a commercial reverse-transcription polymerase chain reaction assay, peripheral blood T-cell subpopulations assessed by flow cytometry, and chemokine levels quantified using commercial sandwich enzyme-linked immunosorbent assay kits.

RESULTS

Following initiation of indinavir-based therapy, significant decreases in plasma HIV-RNA levels (change = 2.0 +/- 0.75 log 10 copies/ml) were observed in conjunction with significant increases in absolute CD4+ (change = 83 +/- 19 cells x 10(6)/l) and CD8+ (change = 293 +/- 96 cells x 10(6)/l) T-cell numbers. Concomitantly, significant increases in MIP-1 alpha (19% increase), MIP-1 beta (14% increase), RANTES (15% increase) and IL-16 (1213% increase) levels occurred. In contrast, MCP-1 levels decreased significantly (47% decrease).

CONCLUSION

The in vivo demonstration of an association between diminishing plasma HIV-RNA levels and the emergence of a circulating chemokine profile capable of inhibiting HIV replication corroborates recent in vitro observations and provides evidence for the restoration of chemokine capacity by HIV protease inhibitor-based therapy.