Corticosteroid therapy, vitamin D status, and inflammatory cytokine profile in the HIV-tuberculosis immune reconstitution inflammatory syndrome.

BACKGROUND: Tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS) in patients coinfected with human immunodeficiency virus (HIV) and tuberculosis starting antiretroviral therapy (ART) is associated with hypercytokinemia. As adjunctive corticosteroid therapy and vitamin D have immunomodulatory properties, we investigated the relationship between cytokine/chemokine profiles, corticosteroid use, and vitamin D deficiency in TB-IRIS patients. METHODS: Plasma from 39 TB-IRIS and 42 non-IRIS patients was collected during a prospective study of HIV-associated tuberculosis patients starting ART. In total, 26% of patients received corticosteroid (CTC) therapy pre-ART for severe tuberculosis. Concentrations of total 25-hydroxyvitamin D (25(OH)D) and 14 cytokines/chemokines were determined at ART initiation and 2 weeks later. RESULTS: Patients prescribed concurrent CTC had lower interferon γ (IFN-γ), IP-10, tumor necrosis factor (TNF), interleukin (IL)-6, IL-8, IL-10, IL-12p40, and IL-18 pre-ART (P ≤ .02). TB-IRIS presented at 12 days (median) of ART, irrespective of CTC use. In patients who developed TB-IRIS (not on CTC) IL-6, IL-8, IL-12p40, IL-18, IP-10, and TNF increased during 2 weeks (P ≤ .04) of ART. Vitamin D deficiency (total 25(OH)D <75 nmol/L) was highly prevalent (89%) at baseline. Although vitamin D deficiency at either baseline or 2 weeks was not associated with TB-IRIS, in those not on CTC the median 25(OH)D decreased during 2 weeks (P = .004) of ART. Severe vitamin D deficiency (total 25(OH)D <25 nmol/L) was associated with higher baseline TNF, IL-6, and IL-8 irrespective of IRIS status. CONCLUSIONS: CTC modifies the inflammatory profile of those who develop TB-IRIS. The association between severe vitamin D deficiency and elevated proinflammatory cytokines support a study of vitamin D supplementation in HIV-TB co-infected patients starting ART.

Decrease of vitamin D concentration in patients with HIV infection on a non nucleoside reverse transcriptase inhibitor-containing regimen.

BACKGROUND: Vitamin D is an important determinant of bone health and also plays a major role in the regulation of the immune system. Interestingly, vitamin D status before the start of highly active antiretroviral therapy (HAART) has been recently associated with HIV disease progression and overall mortality in HIV-positive pregnant women. We prospectively studied vitamin D status in HIV individuals on HAART in Belgium.We selected samples from HIV-positive adults starting HAART with a pre-HAART CD4 T-cell count >100 cells/mm3 followed up for at least 12 months without a treatment change. We compared 25-hydroxyvitamin D plasma [25-(OH)D] concentration in paired samples before and after 12 months of HAART. 25-(OH)D levels are presented using two different cut-offs: <20 ng/ml and <30 ng/ml. RESULTS: Vitamin D deficiency was common before HAART, the frequency of plasma 25-(OH)D concentrations below 20 ng/ml and 30 below ng/ml was 43.7% and 70.1% respectively. After 12 months on HAART, the frequency increased to 47.1% and 81.6%.HAART for 12 months was associated with a significant decrease of plasma 25-(OH)D concentration (p = 0.001). Decreasing plasma 25-(OH)D concentration on HAART was associated in the multivariate model with NNRTI-based regimen (p = 0.001) and lower body weight (p = 0.008). Plasma 25-(OH)D concentrations decreased significantly in both nevirapine and efavirenz-containing regimens but not in PI-treated patients. CONCLUSIONS: Vitamin D deficiency is frequent in HIV-positive individuals and NNRTI therapy further decreases 25-(OH)D concentrations. Consequently, vitamin D status need to be checked regularly in all HIV-infected patients and vitamin D supplementation should be given when needed.

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

BACKGROUND: About 20-30% of persons with HIV infection, especially those living in countries with limited resources, experience an immune reconstitution inflammatory syndrome (IRIS) after starting antiretroviral treatment. The active form of vitamin D, 1,25-dihydroxyvitamin D, is a key player in the clearance of pathogens and influences the level of inflammation and macrophage activation. PRESENTATION OF THE HYPOTHESIS: 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. TESTING THE HYPOTHESIS: 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. IMPLICATIONS OF THE HYPOTHESIS: 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.