Combination of CCR5 and CXCR4 inhibitors in therapy of human immunodeficiency virus type 1 infection: in vitro studies of mixed virus infections.
We studied the combined anti-human immunodeficiency virus type 1 (HIV-1) effects of a derivative of stroma-derived factor 1beta (SDF-1beta), Met-SDF-1beta, and a modified form of RANTES, aminooxypentane (AOP)-RANTES. The antiviral agents were tested singly or in combination at 95 and 99% virus inhibitory concentrations. Clinical R5 and X4 HIV-1 isolates were used. AOP-RANTES inhibited R5 but not X4 viruses, whereas Met-SDF-1beta had the opposite effect. Combinations of these compounds inhibited mixed infections with R5 and X4 viruses (95 to 99%), whereas single drugs were less inhibitory (32 to 61%). Combinations of R5 and X4 inhibitors are promising and deserve further evaluation.
Rusconi
S
S
Istituto di Malattie Infettive e Tropicali, Università di Milano, Ospedale Luigi Sacco, Milan, Italy. rusconi@mailserver.unimi.it
La Seta Catamancio
S
S
Citterio
P
P
Bulgheroni
E
E
Croce
F
F
Herrmann
S H
SH
Offord
R E
RE
Galli
M
M
Hirsch
M S
MS
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D065100:CCR5 Receptor Antagonists; D002460:Cell Line; D018946:Chemokine CCL5 / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D054377:Chemokine CXCL12; D016207:Cytokines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D016679:Genome, Viral; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D016207:Cytokines; D019718:Receptors, CXCR4