Short Communication: Plasma Levels of Vitamin D in HIV Patients Initiating Antiretroviral Therapy Do Not Predict Immune Restoration Disease Associated with Mycobacterium tuberculosis

Abstract

Immune restoration disease associated with Mycobacterium tuberculosis (TB IRD) is clinically important among HIV patients commencing antiretroviral therapy in countries where tuberculosis is endemic. Vitamin D affects dendritic cell and T cell function and the antimicrobial activity of monocytes. Plasma levels of vitamin D and polymorphisms in the vitamin D receptor may affect tuberculosis, and HIV infection associates with vitamin D deficiency. Here we assess whether plasma vitamin D levels may predict TB IRD. Samples were available from prospective studies of TB IRD in Cambodia (26 cases), India (19 cases), and South Africa (29 cases). IRD cases and controls from each site were similar in age and baseline CD4(+) T cell count. Plasma samples were assessed using 25(OH) vitamin D immunoassay plates. DNA samples were available from a subset of patients and were genotyped for the VDR FokI (F/f) [C/T, rs10735810] SNP. When data from each cohort were pooled to assess ethnic/geographic differences, 25(OH)D levels were higher in Cambodian than Indian or South African patients (p<0.0001) and higher in South African than Indian patients (p<0.0001). TB IRD was not associated with differences in levels of 25(OH)D in any cohort (p=0.36-0.82), irrespective of the patients' prior TB diagnoses/treatment. Carriage of the minor allele of VDR FokI (F/f) was marginally associated with TB IRD in Indian patients (p=0.06) with no association in Cambodians. Neither plasma levels of vitamin D nor the vitamin D allele will usefully predict TB IRD in diverse populations from TB endemic regions.

Vitamin D status and risk of incident tuberculosis disease: A nested case-control study, systematic review, and individual-participant data meta-analysis

“…After screening titles and abstracts, we excluded 2,678 articles because they were reviews, meta-analyses, letters, editorials or protocols ( n = 1,212), case reports ( n = 515), studies of other diseases or other outcomes ( n = 331), animal or in vitro studies ( n = 247), case-control or cross-sectional studies that assessed vitamin D status after TB disease diagnosis ( n = 159), studies that did not measure vitamin D ( n = 144), studies of TB treatment outcomes ( n = 63), and studies of TB infection ( n = 7) (Fig 2). We reviewed full texts of the remaining 11 articles [28–38] and further excluded three studies that assessed outcomes of TB-IRIS [35–37] and one study of TB infection with seasonality of TB [38]. Table 5 provides information about the seven eligible published studies [28–34] identified from the systematic review through December 31, 2017.…”

Paradoxical TB-IRIS in HIV-infected Adults: a Systematic Review and Meta-analysis

“…It has been proposed that vitamin D deficiency may predispose to TB-IRIS [67] and this would then place those at higher latitudes at greater risk of TB-IRIS. However, studies to date have not confirmed an association between baseline vitamin D status and IRIS risk [68,69].…”

Vitamin D Status and Its Consequences for Health in South Africa

“…Seasonal vitamin D deficiency was significantly associated with disease or HIV-1 replication in three studies from the Western Cape [38,64,65], with vitamin D deficiency more severe in patients co-infected with HIV-1 and Mycobacterium tuberculosis [64]. Three multinational cohort studies which included participants from Gauteng and/or KwaZulu-Natal also found vitamin D deficiency in approximately 40%–50% of HIV-1-infected patients, but there was no control comparison group so that disease association could not be assessed [67,68,69]. Participants from the PEARLS (Prospective Evaluation of Antiretrovirals in Resource Limited Settings) trial were used in two of these studies.…”