A Mathematical Model for the Treatment of Aids-Related Kaposi's Sarcoma

Abstract

We formulate a mathematical model to study the dynamics of HIV-1 related Kaposi's Sarcoma (KS) pathogenesis. KS progression is modeled as a dual process involving the primary infection of B cells, which sustains HHV-8 replication and the secondary infection of progenitor cells by HHV-8, which sustains the KS cell replication. We incorporate the pharmacodynamics of highly active antiretroviral therapy (HAART), or combination therapy (HAART plus KS therapy) and consider how each treatment strategy alters the disease progression. Our results indicate that administration of HAART to individuals co-infected with the HIV-1 and HHV-8 viruses can greatly amplify the therapeutic response of low-dose KS therapies. We have found that adherence levels above 85% can significantly reduce the risk of KS and HIV for a treatment periods under 1 year. For longer treatment periods, however, at least 90% adherence level is recommended.

A novel mathematical model of AIDS-associated Kaposi's sarcoma: Analysis and optimal control

“…Chang et al [6] identified the herpesvirus-like DNA sequences in AIDS-KS. This study [6] as well as other studies for example [44] showed that AIDS-KS depends upon prior infection to HHV-8. In competent immune systems, however, acquisition of HHV-8 does not necessarily guarantee the development of KS, as many people can remain latently infected with HHV-8 throughout their entire life without developing clinical symptoms [14].…”

“…Nevertheless, only a very few KS mathematical models describing within-host dynamics have been published. The few examples include the mathematical models by Nani and Jin [30,31] and Szomolay and Lungu [44]. The study of Nani and Jin's [30,31] describes the dynamics of AIDS-KS during HAART, concluding that both HAART and adoptive immunotherapy are necessary to annihilate both HIV and KS.…”

“…The study of Nani and Jin's [30,31] describes the dynamics of AIDS-KS during HAART, concluding that both HAART and adoptive immunotherapy are necessary to annihilate both HIV and KS. The framework developed by Szomolay and Lungu [44] included the adaptive immune system and the effect of adhering to cART therapy. Their findings established that adherence to treatment has a significant impact on the prognosis of KS.…”

Effect of innate and adaptive immune mechanisms on treatment regimens in an AIDS-related Kaposi's Sarcoma model

“…Figure 2 shows the sensitivity analysis demonstrating how the model parameters are correlated to the reproduction number, R 0 . We have found that the rate of infected B-cell proliferation, K 2 , is positively and significantly correlated with the reproduction number, a conclusion supported Maximum carrying capacity of infected B cells 700 [31] by experimental observations by [13]. The other model parameters are not significantly correlated to R 0 , and their effect on disease progression is peripheral.…”

“…The development of each of these forms is dependent on prior infection with HHV-8. However, HHV-8 infection alone is insufficient for the development of KS and some form of immunodeficiency is necessary for disease progression [31].…”