Is vitamin D deficiency involved in the immune reconstitution inflammatory syndrome?

We hypothesize that low availability of 1,25-dihydroxyvitamin D, either due to vitamin D deficiency or due to polymorphisms in the vitamin D receptor or in its activating/inactivating enzymes, contributes to the appearance of IRIS. Furthermore, drug interactions with the enzymatic pathways of vitamin D could favour the development of IRIS.Our hypothesis could be explored by a case-control study to assess the prevalence of vitamin D deficiency in HIV-infected patients on antiretroviral treatment who develop and do not develop IRIS.If the role of vitamin D in IRIS is confirmed, we would be able to screen patients at risk for IRIS by screening for vitamin D deficiency. After confirmation by means of a clinical trial, vitamin D supplementation could be a cheap and safe way to reduce the incidence of IRIS.Highly active anti-retroviral therapy (HAART) decreases the mortality and improves the quality of life of persons living with human immunodeficiency virus (HIV) infection [1]. Nevertheless, 17–32% of HIV infected persons living in countries with limited resources experience a temporary worsening of their clinical status after starting HAART despite immunological improvement [2,3]. This paradoxical reaction occurs most frequently during the first 3 months after initiation of HAART and is known as immune reconstitution inflammatory syndrome (IRIS) or immune restoration disease (IRD) [4]. To date, more than 20 different pathogens have been associated with IRIS [2,3,5,6]. However, IRIS has also been described in association with autoimmune diseases, cancer, and some non-infectious granulomatous diseases such as sarcoidosis and Crohn's disease [7].In countries with limited resources, Mycobacteria sp. are by far the most common pathogens involved [5].There is now evidence that vitamin D plays a role in improving anti-tuberculosis immunity as well as in the regulation of immune responses [8-11], both of which are crucial steps in the development of IRIS. A double blind randomi