Positive influence of the Delta32CCR5 allele on response to highly active antiretroviral therapy (HAART) in HIV-1 infected patients.
The heterozygous 32 base pair deletion of the chemokine receptor 5 (Delta32CCR5) has been associated with a more benign course of HIV-1-infection. To study the influence of Delta32CCR5 on the response to antiviral therapy we analyzed the presence of Delta32CCR5 by PCR in PBMC from 107 randomly selected HIV-1-infected patients treated with HAART for at least three months. 24 of 107 patients were heterozygous for Delta32CCR5 (22.4%). Before initiation of HAART Delta32CCR5 heterozygous patients (d/w) did not differ from homozygous CCR5 wild-type patients (w/w) regarding viral load and CD4 counts. After a median treatment time on HAART of 17.5 months (d/w, range 6-31 months, p = n.s.) or 19 months (w/w, range 3-33 months) all 24 patients (100%) with the Delta32CCR5 mutation, but only 58/83 patients (69.9%) with wild-type CCR5 showed a suppression of HIV-1-viremia below 500 copies/ml (p = 0.0020). Furthermore, 20/24 (83.3%) of the Delta32CCR5 heterozygous patients achieved CD4 counts above 200/microliter, but only 57/83 (68.7%) of the patients homozygous for CCR5 wild-type (p = 0.011). Our data indicate that the presence of heterozygous Delta32CCR5 is associated with a better response to HAART suggesting that therapeutic strategies targeting CCR5 could be of value for a sustained suppression of HIV-1 by HAART.
Kasten
S
S
Department of Medicine III, University of Erlangen-Nuremberg, Krankenhausstrasse 12, D-91054 Erlangen, Germany.
Goldwich
A
A
Schmitt
M
M
Rascu
A
A
Grunke
M
M
Dechant
C
C
Kalden
J R
JR
Harrer
T
T
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000235:genetics*; D000483:Alleles; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D015224:Dideoxynucleosides / Q000627:therapeutic use*; D004352:Drug Resistance, Microbial / Q000235:genetics; D005260:Female; D015497:HIV-1; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D019713:Receptors, CCR5 / Q000235:genetics*; D015215:Zidovudine / Q000627:therapeutic use; D000099227:Abacavir
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D019259:Lamivudine; D019713:Receptors, CCR5; D015215:Zidovudine; D000099227:Abacavir