Influence of a monocyte chemoattractant protein 1 mutated allele on the response to protease inhibitor-based antiretroviral therapy.
BACKGROUND
Antiretroviral drug efficacy has been widely studied in relation to viral factors. Mutations in the HIV co-receptors and their natural chemokines, however, may be critical in HIV infection and treatment response. We compared the efficacy of protease inhibitor (PI) treatment among PI-naïve patients grouped according to whether they carried the chemokine CC motif receptor 2 (CCR-2) 64I and monocyte chemoattractant protein 1 (MCP-1)-2518G alleles.


RESULTS
HIV-infected patients who were PI-naive were selected for the study (n=164) but there was no restriction on lymphocyte CD4 count or plasma HIV viral load. Follow-up was for the first 24 months of treatment. Clinical and laboratory data were obtained every 3 months. All the participants were genotyped for the MCP-1-2518G, CCR-2 64I, CCR-5Delta32 and stromal derived factor 1 (SDF1) 3'A mutated alleles. The results indicated that patients carrying the mutated allele of MCP-1 had a higher mean CD4 cell count throughout the follow-up period than those with the common allele (P=0.01). Also, patients with the MCP-1 and CCR-2 mutated alleles were more likely to continue to have an undetectable viral load following treatment (P=0.05).


CONCLUSIONS
A better response to PI treatment appears to be conferred by mutations in the host MCP-1 and CCR-2 genes, and may be related to the cellular axis-of-entry used by the retrovirus.
Coll
B
B
Servei de Medicina Interna, Hospital Universitari de Sant Joan, Reus, Spain. bcoll@grupsagessa.com
Alonso-Villaverde
C
C
Parra
S
S
Rabassa
A
A
Martorell
L
L
Joven
J
J
Masana
L
L
D000328:Adult; D000368:Aged; D000483:Alleles; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D018932:Chemokine CCL2 / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000235:genetics; D016896:Treatment Outcome; D019562:Viral Load
C515334:CCR2 protein, human; D018932:Chemokine CCL2; D017320:HIV Protease Inhibitors; D054390:Receptors, CCR2; D019707:Receptors, Chemokine