This thesis examines the impact of HIV superinfection (infection of HIV-positive
individuals by a heterologous HIV strain after immune responses have been
established against the first strain) upon HIV disease progression and viral blips, and
the relationship between non-adherence to cART and the occurrence of viral blips.
For these purposes, a mathematical model of HIV within-host dynamics with two
strains has been developed.
My results suggest: firstly, HIV superinfection in and of itself was found not leading
to faster progression to AIDS; it is only superinfection with strains of a higher
replication capacity that does. Secondly, it was found that superinfecting strains
susceptible to the existing cART regimen cannot establish themselves in patients,
while those resistant to the regiment will lead to treatment failure. Superinfection in
either scenario will not lead to viral blips. Thirdly, the choice of sampling frame was
found to have a significant impact upon the observed number and incidence of viral
blips. Instead of calculating the incidence of blips from their observed number over a
period of time, one should take into account the sampling frame and calculate the
proportion of blips among the measurements made over that period. Fourthly,
increased drug adherence three days before a clinic visit does not mask poor
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adherence; regular consecutive non-adherence results in more blips than a random
non-adherence pattern; and dose-timing variation around the regimen-prescribed time
leads to more blips. Fifthly, the non-linear relationship between the proportion of
measurements with detectable viral blips and the probable drug adherence of a patient,
and how this relationship varies with the viral replication rate, are studied.
This thesis improves our understanding of anti-HIV immune responses, refines our
public health messages and provides us with indications of drug adherence through
observation of viral blips with different sampling frames.