Abstract:
Kaposi’s sarcoma is a common AIDS-defining cancer that has continued to afflict
patients living with HIV-1, especially, individuals who are currently not on HAART
or whose HIV-1 status is not known. Even individuals who have had a prior HHV-8
infection and are on HAART are at an increased risk of developing KS whenever drug
failure occurs and when one develops drug resistance to the drugs being administered.
Like other herpesvirus, KS associated herpesvirus (KSHV), also known as human
herpesvirus-8 (HHV-8) is a lifelong infection in a host. The non-AIDS related KS is
less life threatening than the HIV related KS.
In this study, we first develop a mathematical model for the development of Classic
KS that involves the interaction of infected B cells, infected progenitor cells, KS
cells, HHV-8 virions and the innate immune response. The innate immune signalling
molecules generated in response to viral infection lead to the production of a broad
range of antiviral proteins and cytokines that generate the initial fight back against
the infection. From this model we shall show that KS therapy alone is capable of
reducing the HHV-8 load and consequently the tumor burden is diminished.
The innate response above is followed by an adaptive immune response which is a more robust response involving the killer T cells. The adaptive immunity is the second arm of the immune response that is elicited following the failure of the innate immunity
to clear an infection. We have also incorporated three controls to explore the roles
of HAART and anti-KS therapy in reducing the burden of AIDS-KS infection. From
the model we show that if HAART is administered at optimal levels, both HIV-1 and
HHV-8 can be reduced to undetectable levels.
In the second model, we have developed a mathematical model for non-AIDS-related
KS (NAKS) that encompasses uninfected B and progenitor cells, HHV-8 specific
effector cells, immune response that is tailored toward viral suppression, latently and
lytically infected B cells, infected progenitor cells, Kaposi’s sarcoma cells and HHV-8.
The motivation of this study comes from the realization that little attention has been
paid towards finding treatment options to inhibit reactivation of lytic replication of
HHV-8 and other therapies to reduce infection of B cells by HHV-8. It is therefore
imperative that efficacious drugs are developed to ease the affliction of NAKS patients.
Unlike AIDS-related KS, NAKS variant normally results is an indolent tumor that
individuals can live with throughout their lives. However, sometimes the cancer
cells can spread to other internal organs in the host where metastasis can be life
threatening. Due to increasing cases being recorded in sub-Sahara Africa, there is an
urgency to develop new drugs and to recommend ways to increase the efficacies of
some already existing drugs for this cancer. This study has recommended the range
of efficacies that we believe can adequately clear the KS infection, provided adherence
protocols are maintained to avoid the emergence of drug resistance.
The predictions of these mathematical model have the potential to offer more effective
therapeutic interventions in the treatment of NAKS or AIDS-related KS (AKS
Mulenga, C (2024). The Pathogenesis of AIDS-related and non-AIDS-related KS: A mathematical perspective,. Afribary. Retrieved from https://afribary.com/works/the-pathogenesis-of-aids-related-and-non-aids-related-ks-a-mathematical-perspective
Mulenga, Chimbola "The Pathogenesis of AIDS-related and non-AIDS-related KS: A mathematical perspective," Afribary. Afribary, 30 Mar. 2024, https://afribary.com/works/the-pathogenesis-of-aids-related-and-non-aids-related-ks-a-mathematical-perspective. Accessed 14 Oct. 2024.
Mulenga, Chimbola . "The Pathogenesis of AIDS-related and non-AIDS-related KS: A mathematical perspective,". Afribary, Afribary, 30 Mar. 2024. Web. 14 Oct. 2024. < https://afribary.com/works/the-pathogenesis-of-aids-related-and-non-aids-related-ks-a-mathematical-perspective >.
Mulenga, Chimbola . "The Pathogenesis of AIDS-related and non-AIDS-related KS: A mathematical perspective," Afribary (2024). Accessed October 14, 2024. https://afribary.com/works/the-pathogenesis-of-aids-related-and-non-aids-related-ks-a-mathematical-perspective