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

Reena Rajasuriar, David Booth, Ajantha Solomon, Kyra Chua, Tim Spelman, Maelenn Gouillou, Timothy E. Schlub, Miles Davenport, Suzanne Crowe, Julian Elliott, Jennifer Hoy, Christopher Fairley, Graeme Stewart, Paul Cameron, Sharon R. Lewin

Research output: Contribution to journalArticlepeer-review

108 Scopus citations

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 α (IL-7Rα) gene were important for immune recovery. Methods. We examined HIV-infected patients receiving suppressive ART (n = 96) for their IL-7Rα 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-7Rα were measured in HIV-infected patients with IL-7Rα haplotype 2 (n = 11) and those without IL-7Rα 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/μL. 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/μL 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-7Rα 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-7Rα levels compared with those of patients without haplotype 2 (P < .001). Conclusion. Both the extent of immune depletion prior to ART and IL-7Rα haplotype 2 are important determinants of time to CD4+ T cell recovery to counts of 1500 cells/μL.

Original languageEnglish
Pages (from-to)1254-1264
Number of pages11
JournalJournal of Infectious Diseases
Volume202
Issue number8
DOIs
StatePublished - 15 Oct 2010
Externally publishedYes

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