No evidence of autoimmune disorders in antiretroviral-experienced HIV-1-infected individuals after long-term treatment with raltegravir.

BACKGROUND: The HIV integrase inhibitor raltegravir (RAL) can exacerbate autoimmune diseases in genetically predisposed mice. To evaluate whether this may occur in clinical practice, we clinically monitored HIV-positive patients treated with RAL and measured a panel of autoantibodies (auto-Abs) during the first year of RAL treatment. METHODS: This was a longitudinal study in 109 antiretroviral-experienced patients who started a RAL-based regimen and were followed up for more than 2 years. A total of 45 patients were tested at baseline (before starting RAL) and after 12 months for the presence of the following auto-Abs: anti-nuclear antibodies, anti-double-stranded DNA, anti-smooth-muscle antibodies, anti-thyreoglobulin and anti-thyroid peroxidase antibodies, anti-cardiolipin immunoglobulin G and immunoglobulin M and anti-nuclear extractable antigens, including anti-SM ribonucleoprotein antigen, anti-Ro antigen and anti-La antigen. RESULTS: A low rate of clinically relevant autoimmune diseases was observed at study entry (3/109; 2.8%; 95% CI 0.004, 0.059). No exacerbations were observed during follow-up. During the second year of RAL-based therapy a previously healthy patient developed psoriasis. At baseline, 17/45 (37.8%) patients tested for the presence of auto-Abs were positive. Most patients (n=13) were positive for anti-cardiolipin. After 12 months of RAL exposure, 9/45 patients were positive (20%; P=0.063). A positive correlation was found between HIV-1 RNA and anti-cardiolipin antibody concentration (P=0.010). CONCLUSIONS: According to these results, RAL does not promote antibody-mediated immune disorders, at least not in the mid-term. A prolonged follow-up and an extension of the panel of auto-Abs are recommended to support these results.

The driving brain: the CNS in the pathogenesis and treatment of anorexia-cachexia syndrome.

Over the past few years, medical care has dramatically improved knowledge of the pathogenic mechanisms of diseases, leading to more effective therapies as well as improved technologies, yielded to enhance survival for diseases that, just a few decades ago, would have been considered lethal. Unfortunately, not all diseases can be completely defeated. In many circumstances, therapies may delay the progression of the disease, leading to improved survival but bringing new issues to light. Of particular interest are nutritional and metabolic alterations due to both prolonged clinical course of disease and long-term therapies. Anorexia-cachexia syndrome often complicates the course of chronic illnesses. Anorexia (i.e., loss of appetite) and cachexia (i.e., loss of weight due to lean body mass and fat-mass wasting) are both associated with a number of diseases. The aim of this article is to highlight the clinical impact of the anorexia-cachexia syndrome and to review current and future etiologic therapeutic approaches.