Mathematical modelling studies of the role of superinfection and non adherence HIV disease progression and viral blips

Abstract

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 6 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.