Discussion
HIV disease, co-infections, Histoplasmosis, HHV-8 viremia, KICS, infections, syphilis, HHV-8, CMV chorioretinitis, ill
VIRUS, HIV DISEASE, HISTOPLASMOSIS, DISEASE, INFECTIONS, CRYPTOCOCCAL MENINGITIS, SYPHILIS, PULMONARY INVOLVEMENT, PATHOGENESIS, IMMUNODEFICIENCY
In this randomized clinical trial, we evaluated the effect of valganciclovir on DKS patients who were cART naïve, with severe immunosuppression, comorbid coinfections, and variable levels of HHV-8 viremia. We found a non-significant lower KS attributable mortality (Several inflammatory cytokines promote the lytic phase of the virus, including [HIV-induced -immunodeficiency; a In this cohort, we found a high prevalence of multiple infections including syphilis (25%), Histoplasmosis and Valganciclovir diminishes HHV-8 VL reducing inflammatory cytokine release when immune reconstitution starts after cART initiation. In Patients with extended disease or Severe-IRIS-KS were treated with 2 mg vincristine and 15 UI bleomycin. This regime was well tolerated; it is not myelosuppressive and does not require concomitant administration of steroids, a recognized amplifier of KS proliferating signaling [The delay in the initiation of cART while giving an anti-HHV8 agent has the same basis as when cART initiation is delayed in CMV chorioretinitis or cryptococcal meningitis, [Our definition of Severe-IRIS-KS shares similarities to KICS criteria [DKS patients typically have high mortality, particularly those with pulmonary involvement [We acknowledge some limitations in our study. First, the sample size was small as we overestimated the expected impact of valganciclovir treatment on mortality, and this may explain a mostly negative trial. The studied patients arrived with advanced HIV disease, severely immunosuppressed, an unlikely situation in high-income countries but not in middle and low-income countries where late HIV diagnosis is still an important proportion of newly diagnosed HIV-infected patients. Patients like those described here are likely found in many other middle and low-income countries still nowadays.However, the trial even if considered a pilot study, leads to several interesting new avenues for this group of severely ill patients, including the utility to perform a thorough investigation of co-infections, measuring the viral load of HHV-8 and utilizing an antiviral agent that inhibits its replication.From our perspective is important in patients with DKS to address four elements of KS pathogenesis when initiating treatment: (1) Exhaustive search and treatment of co-infections (2) control of HHV-8 viremia with valganciclovir (or another anti-HHV8 active agent) [