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.

The predictive value of cerebrospinal fluid Epstein-Barr viral load as a marker of primary central nervous system lymphoma in HIV-infected persons.

BACKGROUND: The presence of Epstein-Barr virus (EBV) DNA in cerebrospinal fluid (CSF) is used as a marker of HIV-associated primary central nervous system lymphoma (PCNSL). In our setting, EBV DNA is frequently detected in the CSF of HIV-infected patients with miscellaneous neurological diseases and thus its presence is a poor predictor of PCNSL. OBJECTIVES: To determine whether quantification of EBV DNA in CSF improves its diagnostic specificity for PCNSL. STUDY DESIGN: EBV viral loads were determined on CSF samples from 55 HIV-infected patients with CNS disease. RESULTS: Twenty of the 55 patients had detectable EBV DNA in their CSF (median viral load 6120copies/ml, range 336-1,034,000copies/ml). PCNSL was confirmed in 2 patients. Their CSF EBV loads were 1,034,000 and 15,460copies/ml, respectively. Using a cut-off of 10,000copies/ml improved the specificity and positive predictive value (PPV) compared to a qualitative result for the diagnosis of PCNSL (96% vs. 66% and 50% vs. 10%, respectively). CONCLUSION: EBV DNA is commonly detected in CSF of HIV-infected patients. Quantitative PCR improves the diagnostic specificity, however, the PPV remains too low for it to be used as an isolated marker for PCNSL.