Approval SheetDefining the Effects of Virus Characteristics and Host Genetic Factors on HIV-1 Viral Fitness and Virulence After HIV-1 Transmission Öffentlichkeit
Yue, Ling (2011)
Abstract
Introduction:
Previous studies suggest that viral load in newly infected
individuals is dependent on viral characteristics in the
chronically infected donors.
Further evidence has confirmed that host genetic factors, such as
human
leukocyte antigen (HLA) molecules, play an important role in immune
control of
HIV-1 infection. The main goal of this study is to determine the
effects of virus
characteristics and host genetic factors on HIV-1 viral fitness and
virulence after
HIV-1 transmission in a Zambian heterosexual transmission
cohort.
Methods: Nested case-control studies were conducted within a
Zambian HIV-1
heterosexual transmission cohort. The 195 epidemiologically linked
transmission
couples who comprised the case group and the 23 unlinked couples
who
comprised the reference group were enrolled from 1995-2006.
Favorable and
unfavorable HLA alleles were selected based on previous studies
both in this
Zambian cohort and other cohort studies in the general population.
Multivariable
generalized linear models (GLM) were used to compare the
simultaneous,
independent contributions of individual genetic and non-genetic
factors to the
variability in HIV-1 viremia. The partial correlations between
donor viral load at
the time of transmission and recipient viral load at set-point were
assessed by
Pearson Correlation analysis.
Results: In the epidemiologically linked transmission group,
seroconverters were
younger than transmitters and the male/female sex ratio of
Transmitters/Seroconverters was >1. Favorable and unfavorable
HLA markers in
both partners were found in a relatively equal distribution. The
Final GLM model
revealed in linked transmission couples that donor viral load is
able to modestly
increase the recipients VL set-point; however, the presence of
favorable HLA
markers and being female are the major effectors for lowering VL
set-point in an
HIV-1 newly infected recipient. When controlling for age, gender,
and
favorable/unfavorable HLA markers, the correlation between donor VL
at the time
of transmission and linked-recipient set-point VL is highly
significant (P< 0.001).
The VL correlation between unlinked couples in the reference group
was not
statistically significant.
Conclusion: Our studies show that protective HLA alleles are
the major driving
force in establishing set-point VL in individuals newly infected
with HIV-1.
However, donor VL at the time of transmission also has a modest
effect on
establishing set-point VL in linked recipients, and females
generally have lower
set-point viral loads than males.
Table of Contents
Table of Contents
Introduction...................................................................................1-3
Background...................................................................................4-12
Significance...................................................................................13-13
Methods.........................................................................................14-19
Results...........................................................................................20-22
Discussion.....................................................................................23-26
Reference.......................................................................................27-31
Tables.............................................................................................32-38
Figures...........................................................................................39-40
Appendix........................................................................................41-41
About this Master's Thesis
School | |
---|---|
Department | |
Degree | |
Submission | |
Language |
|
Research Field | |
Stichwort | |
Committee Chair / Thesis Advisor | |
Committee Members |
Primary PDF
Thumbnail | Title | Date Uploaded | Actions |
---|---|---|---|
Approval SheetDefining the Effects of Virus Characteristics and Host Genetic Factors on HIV-1 Viral Fitness and Virulence After HIV-1 Transmission () | 2018-08-28 10:27:50 -0400 |
|
Supplemental Files
Thumbnail | Title | Date Uploaded | Actions |
---|