Targeted therapy for Kaposi??s sarcoma and Kaposi??s sarcoma-associated herpesvirus

To summarize major recent findings on the biology of human herpesvirus-8, i.e. Kaposi’s sarcoma-associated herpesvirus, and the implications of these findings for Kaposi’s sarcoma treatment

Risk of Cancer among Commercially Insured HIV-Infected Adults on Antiretroviral Therapy.

The objective of this study was to explore the cancer incidence rates among HIV-infected persons with commercial insurance who were on antiretroviral therapy and compare them with those rates in the general population. Paid health insurance claims for 63,221 individuals 18 years or older, with at least one claim with a diagnostic code for HIV and at least one filled prescription for an antiretroviral medication between January 1, 2006, and September 30, 2012, were obtained from the LifeLink® Health Plan Claims Database. The expected number of cancer cases in the general population for each gender-age group (<30, 30-39, 40-49, 50-59, and >60 years) was estimated using incidence rates from the Surveillance Epidemiology and End Results (SEER) program. Standardized incidence ratios (SIRs) were estimated using their 95% confidence intervals (CIs). Compared to the general population, incidence rates for HIV-infected adults were elevated (SIR, 95% CI) for Kaposi sarcoma (46.08; 38.74-48.94), non-Hodgkin lymphoma (4.22; 3.63-4.45), Hodgkin lymphoma (9.83; 7.45-10.84), and anal cancer (30.54; 25.62-32.46) and lower for colorectal cancer (0.69; 0.52-0.76), lung cancer (0.70; 0.54, 0.77), and prostate cancer (0.54; 0.45-0.58). Commercially insured, treated HIV-infected adults had elevated rates for infection-related cancers, but not for common non-AIDS defining cancers

Rapamycin With Antiretroviral Therapy in AIDS-Associated Kaposi Sarcoma: An AIDS Malignancy Consortium Study

The mammalian target of rapamycin (mTOR) is activated in Kaposi sarcoma (KS) and its inhibitor, rapamycin, has induced KS regression in transplant-associated KS. This study aimed to evaluate rapamycin's safety and toxicity in HIV-infected individuals with KS receiving antiretroviral therapy (ART), investigate rapamycin interactions with both protease inhibitor (PI)-containing and non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing ART regimens, and assess clinical and biological endpoints including KS response and mTOR-dependent signaling

Molecular and Clinical Assessment in the Treatment of AIDS Kaposi Sarcoma with Valproic Acid

The AIDS Malignancy Consortium (AMC) undertook a pilot trial of valproic acid (VA) in patients with AIDS-associated Kaposi’s sarcoma (KS). Treatment was associated with low toxicity, but the KS clinical response and KS herpesvirus lytic induction rates were not sufficiently high to meet pre-defined criteria for efficacy

A phase 1b/pharmacokinetic trial of PTC299, a novel post-transcriptional VEGF inhibitor, for AIDS-related Kaposi’s sarcoma: AIDS Malignancy Consortium trial 059

Vascular endothelial growth factor (VEGF) plays an important role in Kaposi’s sarcoma (KS). We administered PTC299, a post-transcriptional inhibitor of pathogenic VEGF, to persons with HIV-related KS. Seventeen participants received three different doses of PTC299. Adverse events typically observed with VEGF-inhibition were absent. Three participants had partial tumor responses and 11 had stable disease. There were no differences in exposure to PTC299 by antiretroviral regimen. Serum VEGF, but not KSHV DNA, decreased on treatment. Given redundancies in the VEGF feedback loop, future trials should consider combining PTC299 with agents that inhibit different pathways implicated in KS and KSHV proliferation

Kaposi sarcoma

Kaposi sarcoma (KS) gained public attention as an AIDS-defining malignancy; its appearance on the skin was a highly stigmatizing sign of HIV infection during the height of the AIDS epidemic. The widespread introduction of effective antiretrovirals to control HIV by restoring immunocompetence reduced the prevalence of AIDS-related KS, although KS does occur in individuals with well-controlled HIV infection. KS also presents in individuals without HIV infection in older men (classic KS), in sub-Saharan Africa (endemic KS) and in transplant recipients (iatrogenic KS). The aetiologic agent of KS is KS herpesvirus (KSHV; also known as human herpesvirus-8), and viral proteins can induce KS-associated cellular changes that enable the virus to evade the host immune system and allow the infected cell to survive and proliferate despite viral infection. Currently, most cases of KS occur in sub-Saharan Africa, where KSHV infection is prevalent owing to transmission by saliva in childhood compounded by the ongoing AIDS epidemic. Treatment for early AIDS-related KS in previously untreated patients should start with the control of HIV with antiretrovirals, which frequently results in KS regression. In advanced-stage KS, chemotherapy with pegylated liposomal doxorubicin or paclitaxel is the most common treatment, although it is seldom curative. In sub-Saharan Africa, KS continues to have a poor prognosis. Newer treatments for KS based on the mechanisms of its pathogenesis are being explored