Publications & Reports

Biological determinants of immune reconstitution in HIV-infected patients receiving antiretroviral therapy: the role of interleukin 7 and interleukin 7 receptor alpha and microbial translocation.

Rajasuriar R, Booth D, Solomon A, Chua K, Spelman T, Gouillou M, Schlub TE, Davenport M, Crowe S, Elliott J, Hoy J, Fairley C, Stewart G, Cameron P, Lewin SR
Department of Medicine, Monash University, Burnet Institute, University of Melbourne, Melbourne, Australia.

Abstract

BACKGROUND: Multiple host factors may influence CD4(+) T cell reconstitution in human immunodeficiency virus (HIV)-infected patients after suppressive antiretroviral therapy (ART). We hypothesized that residual immune activation and polymorphisms in the interleukin 7 (IL-7) receptor alpha (IL-7Ralpha) gene were important for immune recovery. METHODS: We examined HIV-infected patients receiving suppressive ART (n = 96) for their IL-7Ralpha haplotypes and measured levels of lipopolysaccharide (LPS), soluble CD14, and IL-7 in plasma samples collected before and after ART initiation. Levels of soluble IL-7Ralpha were measured in HIV-infected patients with IL-7Ralpha haplotype 2 (n = 11) and those without IL-7Ralpha haplotype 2 (n = 22). Multivariate analysis was used to identify variables associated with faster recovery to CD4(+) T cell counts of >500 and >200 cells/muL. RESULTS: Both LPS and soluble CD14 levels were significantly decreased with ART (P < .001, respectively) but remained elevated compared with uninfected controls. In a multivariate analysis, faster recovery to a CD4(+) T cell count of >500 cells/muL was significantly associated with higher baseline CD4(+) T cell count, younger age, lower pre-ART LPS level, higher pre-ART soluble CD14 level, lower pre-ART IL-7 level, and IL-7Ralpha haplotype 2 (hazard ratio, 1.50; 95% confidence interval, 1.03-2.19; P = .034). HIV-infected patients with haplotype 2 had significantly lower soluble IL-7Ralpha levels compared with those of patients without haplotype 2 (P < .001). CONCLUSION: Both the extent of immune depletion prior to ART and IL-7Ralpha haplotype 2 are important determinants of time to CD4(+) T cell recovery to counts of >500 cells/muL.

Publication

  • Journal: The Journal of Infectious Diseases
  • Published: 15/10/2010
  • Volume: 202
  • Issue: 8
  • Pagination: 1254-1264

Authors