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.