Abstract
BackgroundKynurenine/Tryptophan ratio (KTR) is increased in HIV infection, and linked to immune activation. We hypothesized that early cART initiation results in lower KTR compared to late initiation. Furthermore, we hypothesized that KTR prior to cART is a predictor of the magnitude of subsequent reduction in immune activation.MethodsProspective study including 57 HIV-infected individuals (primary HIV infection (N = 14), early presenters (>350 CD4+ T cells/μL, N = 24), late presenters (<200 CD4+ T cells/μL, N = 19)). Kynurenine and tryptophan were analysed by liquid chromatography–tandem mass spectrometry. Total CD4+ and CD8+ T cells were determined and proportion of activated CD38 + HLA-DR+ Tcells was measured using flow cytometry at baseline and after 6 and 12 months of cART.ResultsAt baseline, primary HIV infection had higher KTR than early presenters. However, similar KTR in primary HIV infection and early presenters was found after cART initiation, while late presenters had higher KTR at all time points. In primary HIV infection and early presenters, KTR was positively associated with proportion of activated cells at baseline. Furthermore, in early presenters the KTR at baseline was associated with proportion of activated cells after 6 and 12 months. Interestingly, in primary HIV infection the KTR at baseline was positively associated with reduction in proportion of CD8 + CD38 + HLA-DR T cells after 6 and 12 months.ConclusionsLower kynurenine/tryptophan ratio during follow-up was found after early initiation of cART. KTR in primary HIV infection and early presenters was positively associated with immune activation. Importantly, KTR in primary HIV infection predicted the magnitude of subsequent reduction in immune activation. Thus, a beneficial effect of early cART on KTR was suggested.
Highlights
Kynurenine/Tryptophan ratio (KTR) is increased in HIV infection, and linked to immune activation
The present study extends the knowledge of the impact of KTR in HIV infection by demonstrating that early initiation of combination antiretroviral therapy (cART) is associated with lower KTR set point after 6 and 12 months of cART when compared to initiation of cART with CD4+ T cells counts less than 200 cells/μL
In conclusion, initiation of cART during either primary or early HIV infection had a beneficial effect on KTR set point at follow-up compared to initiation of treatment in late presenting HIV infection
Summary
Kynurenine/Tryptophan ratio (KTR) is increased in HIV infection, and linked to immune activation. Primary HIV infection is characterized by rapid depletion of CD4+ T-cells, high viral load, and the establishment of a chronic state of immune activation [1]. The magnitude of these three events has been shown to be closely related to the long term prognosis in HIVinfected individuals [2, 3]. Minor amounts of IDO-like enzymes are produced by gut bacteria [8] This activity has been described to be enhanced in HIV-infected individuals [8, 9].IDO catalyzes the catabolism of tryptophan to Nformylkynyrenine, which is rapidly decomposed to kynurenine [10, 11].
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