The role of human herpesvirus (HHV) infections and persistent immune activation in antiretroviral therapy-treated HIV infected individuals / Yap Siew Hwei
Co-infections with human herpesvirus (HHV) have been associated with residual chronic inflammation in antiretroviral therapy (ART)-treated human immunodeficiency virus (HIV)-infected individuals. However, the burden of HHV co-infection among HIVinfected individuals is unknown in the developing cou...
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| Format: | Thesis |
| Published: |
2018
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| Online Access: | http://studentsrepo.um.edu.my/11474/4/yap.pdf http://studentsrepo.um.edu.my/11474/ |
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| Summary: | Co-infections with human herpesvirus (HHV) have been associated with residual chronic
inflammation in antiretroviral therapy (ART)-treated human immunodeficiency virus
(HIV)-infected individuals. However, the burden of HHV co-infection among HIVinfected individuals is unknown in the developing country and the role of HHV in
modulating the kynurenine pathway and clinical outcomes in HIV-infected individuals is
poorly understood. Thus, we investigated (1) the seroprevalence of and the risk factors
associated with four common HHVs among treated HIV-infected individuals, (2) the
association of HHV with kynurenine/tryptophan (K/T) ratio and (3) other chronic
immune activation markers and the impact of HHV infection on long-term CD4 T-cell
recovery in HIV/HHV co-infected individuals. In this cross-sectional study, HIV-infected
patients 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), 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. A total of 232 HIV-infected individuals
was 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. Multivariate
analysis revealed that a longer duration on ART was associated with an increased odd of
both HSV-1 (aOR: 1.12; 95% CI: 1.02-1.22) and HSV-2 (aOR: 1.12; 95% CI: 1.04-1.21)
infection. HSV-2 seropositivity was also associated with being female (aOR: 3.03; 95%
CI: 1.31-7.0) and with a history of AIDS defining illness (aOR: 2.01; 95% CI: 1.12- 3.60).
Indian ethnicity was associated with a lower odds of CMV (aOR: 0.17; 95% CI: 0.04-
iv
0.80) and VZV (aOR: 0.26; 95% CI: 0.09-0.71)seropositivity compared to ethnic Chinese.
In addition, higher current CD4:CD8 ratio was also significantly associated with lower
odds of CMV seropositivity (aOR: 0.21; 95% CI: 0.07-0.68). K/T ratio was significantly
positively correlated with antibodies for 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 titers
demonstrating the strongest modulating effect on K/T ratio among the four HHVs. In
multivariate analysis, higher K/T ratio (p=0.03) and increasing number of HHV coinfections (p<0.001) were independently associated with poorer CD4 T-cell recovery
following 12 months of ART initiation. These data suggested that co-infection with
multiple HHV are common among ART-treated HIV-infected participants in the
developing country setting and are associated with persistent immune activation and
poorer CD4 T-cell recovery. |
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