Valganciclovir for Suppression of HHV-8 Four Weeks Prior to Initiation of cART in Patients With Disseminated Kaposi Sarcoma Compare With Standard Therapy, Its Impact on the Development of IRIS and Attributable Mortality

Kaposi sarcoma (KS) is a Human Herpes-8 disease, it has been described as an angioproliferative disease mediated by cytokines in an environment of immunodeficiency and thus associated with HIV infection. Its course has been described as unpredictable; it can be indolent or can be progressive with a fulminant course. Patients with disseminated KS can have an extensive disseminated cutaneous disease with lymphedema and/or lymph node, gastrointestinal or pulmonary involvement, usually associated with low CD4 T cell counts (<100 cells).

High early mortality in patients starting cART has been described in different settings, and it has been attributed to the development of Immune Reconstitution Syndrome KS (IRIS-KS).

In patients developing IRIS-KS the clinical event until now recognized as IRIS-KS: increase in KS lesion, lymphedema or pleural effusion that is associated with CD4 cells increase and the decrease of at least one log of HIV VL does not fully express what threatens patients life. The clinical picture of IRIS-KS that threatens the patient's life is the abrupt development of fever with no other infection recognized, rapid clinical deterioration with thrombocytopenia, anemia, hyponatremia, and hypoalbuminemia together with an increase in KS lesion, lymphedema, or pleural effusion, this clinical picture we have named Severe-Iris-KS.

Patients with AIDS and disseminated KS are at risk of developing severe Immune Reconstitution Syndrome KS (S-IRIS-KS) after the initiation of cART and this has been associated with high mortality.

Ganciclovir and Foscarnet (antivirals) are active in vitro against HHV-8; valganciclovir is a prodrug of ganciclovir, it is an oral formulation.