High HHV-8 viral load (VL) has been associated with severe Kaposi sarcoma (S-KS). KS Immune reconstitution inflammatory syndrome (IRIS) can occur in patients after starting cART with associated high mortality. Ganciclovir has anti-HHV8 activity. Our objective was to investigate if valganciclovir started before cART could diminish HHV-8-VL and reduce the incidence of S-KS-IRIS and its atributable mortality.
ORCT (Clincal Trials NIH ID NCT03296553) of patients with disseminated KS (DKS), approved by IRB, participants signed informed consent. Inclusion criteria: AIDS cART naïve patients with at least two of the following: pulmonary disease, 30 skin lesions, lymphedema, lymph node involvement, GIT involvement. Exclusion criteria: other malignant disease, steroid treatment, active Hepatitis B or C, CMV end-organ disease; and APACHE >15. S-IRIS-KS definition: abrupt clinical exacerbation of KS after starting cART and at least 3 of the following parameters: thrombocytopenia, anemia, hyponatremia, hypoalbuminemia or fever. Experimental group (EG) started valganciclovir 900 mg BID 4 weeks before cART and continued until week 48; control group (CG) started cART at week 0. Treating physician determined Vincristine/Bleomycin administration. Scheduled visits: weeks 0,1,2,4,8,12,16,24, and 48. In each visit HIV-VL, HHV-8 VL (ELITe M GB KIT) CD4 and CD8 count by flow cytometry.
38 patients were randomized, 19 in each group; one patient stopped valganciclovir and was excluded. Three patients died due to S-IRIS-KS in the CG, two died in the EG (opiod overdose and H1NI pneumonia). Four patients developed 12 episodes of S-IRIS-KS in the CG (IR of 0.21 per/100 patient-days), two patients, one episode each in the EG (IR 0.038 per/100 patient-days) p=0.007. In multivariate poisson or negative binomial models, higher-baseline CD4 decreased and higher HHV8-VL increased consistently the risk of S-IRIS-KS; Valganciclovir treatment reduced S-SIRI-KS events (IRR= 0.06, 95%CI 0.004-0.7 p=0.024) and the number of patients with at least one S-IRIS-KS episode (, IRR 0.24, 95%CI 0.03, 2.27, p= 0.21).
Valganciclovir reduced episodes of S-IRIS-KS and its attributable mortality. Measurement of HHV-8 VL may be important in the clinical care of DKS.