Establishing Molecular Epidemiology in Concordant HIV-1 Positive Heterosexual Couples at CVCT Centers in Rwanda and Zambia Open Access

Dennis, Kristine Kay (2012)

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Epidemiologic linkage techniques for the gp41 region of the HIV-1 proviral genome are
established to characterize HIV-1 transmission dynamics among heterosexual couples
with recent transmission events but have unknown validity for chronically infected
couples with differing levels of viral diversification. To determine if the current pair-wise
distance (PWD) cutoffs (Rwanda 5.4%; Zambia 4.6%) are valid for couples who were
both HIV-1 positive (concordant positives) when first tested, a 399 base pair region of
gp41 was sequenced from 12 longitudinally followed recent transmission pairs and 191
concordant positive couples from Rwanda and Zambia for PWD and neighbor-joining
phylogenetic tree linkage analysis.
The PWD of longitudinally followed couples demonstrated 0.33% and 0.28% PWD
change/year across Rwanda and Zambia, respectively, confirming the PWD cutoff for
each country remains valid for approximately 10 years. Linkage
cohabitation were compared with the gold-standard phylogenetic tree linkage status.
Most concordant positive couples had matching linkage status between PWD and
phylogenetic tree analysis with the exception of a few couples from Rwanda (9 of 101)
and Zambia (12 of 90). After comparing median PWD for linked and unlinked couples
between concordant positives and recent seroconverting pairs, linked concordant
positives had significantly higher median PWD than recent seroconverters across both
countries (p<0.05). Unlinked recent seroconverters had a significantly higher median
PWD than unlinked concordant positives only in Zambia (p<0.01). The proportion of
linked concordant positives was 44.6% in Rwanda and 47.8% in Zambia, as compared to
a sample of recent transmission pairs enrolled in couples voluntary counseling and testing
with 80.5% and 77.9% linked in Rwanda and Zambia, respectively.
Across the concordant positive couples from Rwanda and Zambia, the validity of the
current gp41 PWD cutoff was confirmed for epidemiologic linkage analysis. There was a
greater proportion of couples who were unlinked than recent transmission pairs. Through
the characterization of these concordant positive couples who have not received couples
voluntary counseling and testing, we have a sense of the linkage patterns present in the
general population so future behavioral interventions can be more accurately targeted.

Table of Contents

Table of Contents

Chapter I: Background

HIV Prevalence 1

Heterosexual Transmission 1

Rwanda-Zambia HIV Research Group 2

Epidemiologic Linkage 2

Concordant Positive Couples 3

HIV Diversity: Recombination, Superinfection & Hypermutation 4

Chapter II: Manuscript

Abstract 5

Introduction 6

Methods 7

Results 10

Discussion 14

References 19

Figures 23

Supplemental Figures 27

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