Central Data Catalog

Citation Information

Type Thesis or Dissertation - Doctor of Philosophy
Title The Impact of Herpes Therapy on Genital and Systemic immunology
Author(s)
Publication (Day/Month/Year) 2013
URL https://tspace.library.utoronto.ca/bitstream/1807/75242/1/Yi_Tae_Joon_201311_PhD_thesis.pdf
Abstract
HIV infects more than 34 million people globally. Herpes simplex virus type 2 (HSV-2)
has been associated with a 3-fold increase in the rate of HIV acquisition, which may be due to
physical breaks in the mucosal barrier during symptomatic episodes and/or an increased number
of HIV target cells being exposed in the genital tract. Although clinical trials have demonstrated
that herpes suppression in HIV uninfected individuals had no impact on HIV incidence,
acyclovir was associated with a decrease in plasma HIV viral load and delayed disease
progression in HSV-2 co-infected individuals. In addition, many HIV infected individuals
display persistent systemic immune activation, which correlates with disease progression, despite
successful antiretroviral therapy (ART). It is hypothesized that HSV could be one of the drivers
of this activation. To further assess these relationships, my thesis focused on examining the
impact of herpes therapy on genital tract immunology and systemic immune activation in HIV
uninfected women and a comparison of systemic immune activation in individuals co-infected
with HIV and HSV-2 on ART randomized to valacyclovir or placebo.
A randomized, placebo-controlled, double-blinded, cross-over trial was conducted in
HSV-2 infected, HIV uninfected, women using valacyclovir. No differences were observed in
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the number of various HIV target cells in the endocervix between valacyclovir and placebo
phases. Further, valacyclovir had no impact on systemic immune activation in the same cohort.
In a second clinical trial, the role of herpes therapy on systemic immune activation and
inflammation in HIV and HSV-2 co-infected individuals on ART was evaluated. It was
concluded that valacyclovir therapy had no impact on these parameters in this population.
In summary, we were unable to demonstrate that herpes therapy was able to reduce the
number of HIV target cells in the endocervix of HSV-2 infected, HIV uninfected women or
systemic immune activation in either HIV uninfected or HIV infected individuals. These findings
demonstrate that currently available herpes therapy in standard doses does not appear to reverse
the immunological changes associated with HSV-2 infection

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