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.


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).


CONCLUSIONS
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.
Bisset
L R
LR
Division of Clinical Immunology, University Hospital, Zürich, Switzerland.
Rothen
M
M
Joller-Jemelka
H I
HI
Dubs
R W
RW
Grob
P J
PJ
Opravil
M
M
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood* / Q000188:drug therapy / Q000821:virology; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018932:Chemokine CCL2 / Q000097:blood*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000097:blood*; D018925:Chemokines / Q000097:blood; D005260:Female; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use*; D019410:Interleukin-16 / Q000097:blood*; D019402:Macrophage Inflammatory Proteins / Q000097:blood*; D008297:Male; D012367:RNA, Viral / Q000097:blood; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000145:classification / Q000166:cytology; D019562:Viral Load
D019380:Anti-HIV Agents; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; D019410:Interleukin-16; D019402:Macrophage Inflammatory Proteins; D012367:RNA, Viral; D019469:Indinavir