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HIV/Human herpesvirus co-infections: Impact on tryptophan-kynurenine pathway and immune reconstitution
University of Malaya, Malaysia.
University of Malaya, Malaysia.
University of Malaya, Malaysia.
Hoshi University, Japan.
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 10, article id e0186000Article in journal (Refereed) Published
Abstract [en]

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-gamma, 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 (pamp;lt;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.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE , 2017. Vol. 12, no 10, article id e0186000
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Infectious Medicine
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URN: urn:nbn:se:liu:diva-142149DOI: 10.1371/journal.pone.0186000ISI: 000412601800035PubMedID: 29016635OAI: oai:DiVA.org:liu-142149DiVA, id: diva2:1151703
Note

Funding Agencies|High Impact Research/Ministry of Higher Education, Malaysia (HIR/MOHE) [H-20001-E000001]; UMRG [RP029-14HTM]; University of Malaya [PG164-2015B]; Swedish Research Council; Swedish International Development Cooperation Agency; SIDA SARC; VINNMER for Vinnova [A152731]

Available from: 2017-10-24 Created: 2017-10-24 Last updated: 2017-11-29

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