GNB3 C825T polymorphism and response to anti-retroviral combination therapy in HIV-1-infected patients--a pilot study.
METHODS
Analyses were based on a cohort of 55 HIV infected patients whose treatment was changed due to therapy failure. Viral load, CD4+ and CD8+ cell counts were determined before therapy and after 8 weeks and 16-32 weeks, respectively. GNB3 genotyping was performed using Pyrosequencing. Chemotaxis of purified CD4+ cells was quantified in a Boyden chamber using stromal cell-derived factor 1alpha (SDF-1alpha) as a stimulus.


RESULTS
Age gender, route of infection, treatment, and baseline values for viral load and CD4+ and CD8+ cell counts were not associated with GNB3 genotypes (10 TT, 24 TC, 21CC). After 8 weeks of treatment viral load was lowest in TT genotypes (log copies/ml: TT: 1.88 +/- 0.32; TC: 2.49 +/- 0.24; CC: 3.06 +/- 0.22; p = 0.039) and this trend tended to persist until final visit. Unexpectedly, TT genotypes had lowest CD4+ cell counts at final visit (TT: 165.3 +/- 34.0; TC: 414.4 +/- 72.1; CC: 441.5 +/-70.9; p = 0.047). SDF-1alpha-stimulated chemotaxis was reduced in CD4+ cells from HIV-1-infected patients compared to healthy controls. Still cells from TT genotypes displayed strongest chemotaxis.


CONCLUSIONS
This pilot study suggests that the GNB3 C825T polymorphism is associated with short-term success of HAART treatment in HIV-1-infected patients.
Brockmeyer
N H
NH
Klinik für Dermatologie und Allergologie, Ruhr-Universität, Gudrunstrasse 56, D-44791 Bochum, Germany. n.brockmeyer@derma.de
Potthoff
A
A
Kasper
A
A
Nabring
C
C
Jöckel
K-H
KH
Siffert
W
W
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011110:Polymorphism, Genetic; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load / Q000706:statistics & numerical data
C454420:G-protein beta3 subunit; D020962:Heterotrimeric GTP-Binding Proteins