Approval SheetDefining the Effects of Virus Characteristics and Host Genetic Factors on HIV-1 Viral Fitness and Virulence After HIV-1 Transmission Open Access

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

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School	Laney Graduate School
Department	Clinical Research Curriculum Program
Degree	MS
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Immunology
Keyword	HIV Gender HLA Viral Load Transmission
Committee Chair / Thesis Advisor	Hunter, Eric, Emory University
Committee Members	Boring, John R, Emory University McGowan Jr., John E, Emory University Mulligan, Mark, Emory University Allen, Susan A, Emory University

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