HIV/Human herpesvirus co-infections: Impact on tryptophan-kynurenine pathway and immune reconstitution

Yap, S.H. and Abdullah, N.K. and McStea, M. and Takayama, K. and Chong, M.L. and Crisci, E. and Larsson, M. and Azwa, I. and Kamarulzaman, A. and Leong, K.H. and Woo, Y.L. and Rajasuriar, R. (2017) HIV/Human herpesvirus co-infections: Impact on tryptophan-kynurenine pathway and immune reconstitution. PLoS ONE, 12 (10). e0186000. ISSN 1932-6203

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Background: Co-infections with human herpesvirus (HHV) have been associated with residual chronic inflammation in antiretroviral (ART)-treated human immunodeficiency virus (HIV)-infected individuals. However, the role of HHV in modulating the tryptophan-kynurenine pathway and clinical outcomes in HIV-infected individuals is poorly understood. Thus, we investigated the seroprevalence of four common HHVs among treated HIV-infected participants and their impact on kynurenine/tryptophan (K/T) ratio and long-term CD4 T-cell recovery in HIV/HHV co-infected participants. Method: In this cross-sectional study, HIV-infected participants receiving suppressive ART for a minimum of 12 months were recruited from the University Malaya Medical Centre (UMMC), Malaysia. Stored plasma was analyzed for CMV, VZV, HSV-1 and HSV-2 IgG antibody levels, immune activation markers (interleukin-6, interferon-γ, neopterin and sCD14), kynurenine and tryptophan concentrations. The influence of the number of HHV co-infection and K/T ratio on CD4 T-cell recovery was assessed using multivariate Poisson regression. Results: A total of 232 HIV-infected participants were recruited and all participants were seropositive for at least one HHV; 96.1% with CMV, 86.6% with VZV, 70.7% with HSV-1 and 53.9% with HSV-2. K/T ratio had a significant positive correlation with CMV (rho = 0.205, p = 0.002), VZV (rho = 0.173, p = 0.009) and a tendency with HSV-2 (rho = 0.120, p = 0.070), with CMV antibody titer demonstrating the strongest modulating effect on K/T ratio among the four HHVs assessed in SOM analysis. In multivariate analysis, higher K/T ratio (p = 0.03) and increasing number of HHV co-infections (p<0.001) were independently associated with poorer CD4 T-cell recovery following 12 months of ART initiation. Conclusion: Multiple HHV co-infections are common among ART-treated HIV-infected participants in the developing country setting and associated with persistent immune activation and poorer CD4 T-cell recovery.

Item Type: Article
Uncontrolled Keywords: CD14 antigen; Gamma interferon; Immunoglobulin G; Interleukin 6; Kynurenine; Neopterin; Tryptophan; Virus antibody
Subjects: R Medicine
Divisions: Faculty of Medicine
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 31 Jul 2018 04:38
Last Modified: 31 Jul 2018 04:38

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