ABSTRACT
Kaposi's sarcoma (KS) is a rare cutaneous tumor caused by human herpes virus-8 (HHV-8) infection that preferentially develops in case of severe immunosuppression, such as in HIV/AIDS disease. Haptoglobin (Hp), a polymorphic multifunctional plasma protein, exerts several immunomodulatory effects and is characterized by a genetic polymorphism leading to three major phenotypes (Hp 1-1, Hp 2-1 and Hp 2-2). This study investigated the influence of Hp genetic polymorphism on the development of KS in HIV-positive patients. 661 HIV patients were enrolled in the study with a median age of 35 years and a median follow-up time of 57 months. Hp phenotyping was performed using hemoglobin-supplemented starch gel electrophoresis. In case of low Hp concentration high pressure gel permeation chromatography (HPGPC) was used. The Hp 1-1 phenotype was associated with a significant higher risk of KS compared to the combined group of Hp 2-1 and Hp 2-2 patients (p < 0.0005) which remained significant after adjustment for possible confounding variables (age, gender and AIDS status) (p < 0.001). In contrast, the Hp 2-1 phenotype carried the lowest risk. These findings point to the involvement of Hp phenotypes in the pathogenesis of KS, which may be due to a difference in skin immunosurveillance between the Hp phenotypes.
Subject(s)
HIV Infections/genetics , HIV/immunology , Haptoglobins/genetics , Herpesviridae Infections/genetics , Herpesvirus 8, Human/immunology , Sarcoma, Kaposi/genetics , Adult , DNA Mutational Analysis , Female , Follow-Up Studies , Genetic Association Studies , Genetic Predisposition to Disease , HIV/pathogenicity , HIV Infections/complications , HIV Infections/immunology , HIV Infections/metabolism , Herpesviridae Infections/complications , Herpesviridae Infections/immunology , Herpesviridae Infections/metabolism , Herpesvirus 8, Human/pathogenicity , Humans , Immunosuppression Therapy , Male , Polymorphism, Genetic , Risk Factors , Sarcoma, Kaposi/etiology , Sarcoma, Kaposi/immunology , Sarcoma, Kaposi/metabolismABSTRACT
Artemether-lumefantrine is one of the artemisisnin-based combination therapies recommended for treatment of uncomplicated falciparum malaria. The drug combination is highly efficacious against sensitive and multidrug resistant falciparum malaria. It offers the advantage of rapid clearance of parasites by artemether and the slower elimination of residual parasites by lumefantrine. The combination can be used in all populations except pregnant mothers in the first trimester where safety is still uncertain. There are still concerns about safety and pharmacokinetics of the drug combination in children, especially infants, pregnant mothers and drug interactions with mainly non-nucleoside reverse transcriptase inhibitors and protease inhibitors used for HIV therapy.