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    • Introduction CD T cell recovery after

    2021-12-09

    Introduction CD4+ T cell recovery after initiation of combination antiretroviral therapy (cART) is essential for restoring immune function in HIV-positive individuals [1]. However, CD4 recovery is variable and is affected by factors such as biological sex [2], [3], race [4], BMI [5], geographic region [4], intravenous drug use [6], and alcohol use [7]. Nutritional status (especially micronutrient deficiencies) and inflammation are known to affect CD4 number and function [8], [9], [10], but the association between inflammation or nutritional status and CD4 recovery in HIV-positive adults after cART initiation has not been well studied, particularly in low- and middle-income (LMIC) populations, where high levels of malnutrition have been observed. Most people living with HIV are at risk for experiencing malnutrition and inflammation. In particular, undernourishment may worsen HIV outcomes [11]. There is substantial interest in using serum or plasma-based biomarkers to identify patients at risk for HIV progression. Markers of malnutrition and inflammation that have been previously associated with adverse HIV clinical outcomes may also be predictors of CD4 recovery post-cART. Diminished nutritional status, especially micronutrient malnutrition, and inflammation have been associated with CD4 proliferation and function in HIV-positive patients [8], [9], [10]. In particular, micronutrient deficiencies of vitamin B12, vitamin D, selenium, and topotecan australia have antioxidant effects, which have been linked to HIV activation and disease progression in individuals not on cART [11], [12], [13]. Similarly, several markers of inflammation assessed in serum or plasma, including soluble CD14 (sCD14), C-reactive protein (CRP), CXCL10, and interleukin-6 (IL-6), have been associated with increased risk of mortality on cART [14], [15], [16]. However, whether such adverse clinical outcomes are mediated by differences in CD4 reconstitution remains unclear [17], [18], [19].
    Methods
    Results
    Discussion The WHO has long recognized nutrition as an important factor in HIV progression [33]. Micronutrient deficiencies are very common in HIV-positive individuals, and deficiencies in selenium and 25(OH)-vitamin D have been associated with HIV disease progression [9], [34], [35], [36]. However, the effect of micronutrient deficiencies on longitudinal CD4 recovery after cART initiation has not been adequately studied. Our analysis found that lower concentrations of baseline vitamin D are associated with lower long-term CD4 recovery; utilizing a global cohort of participants in this study adds a wider scope to these previously reported results. Both cross-sectional and supplementation studies indicate that, in the context of HIV, vitamin D insufficiency and deficiency can lead to adverse outcomes, such as mortality and progression to AIDS in patients on cART and not on cART [37], [38]. Our group has previously reported in this cohort that baseline Vitamin D insufficiency and deficiency are associated with increased risk of HIV disease progression post-ART initiation [36]; this may be in part related to the reduced CD4 recovery we observed in this analysis and as suggested by other recent studies [39]. Vitamin D sufficiency could potentially help with CD4 recovery as recent studies have shown that vitamin D is essential for immune function. It has been reported that sufficient vitamin D levels can reduce inflammation and T cell activation (both of which have been associated with CD4 loss) while improving the efficiency of antigen presenting cells to induce CD4 T cell proliferation [10], [37], [40]. From a supplementation standpoint, however, the evidence for the association of vitamin D levels and CD4 recovery is not as strong. For instance, a small 2011 study conducted in HIV-positive children on ART in Toronto (n = 54; 75% of whom were vitamin D insufficient or deficient) observed no increase in CD4 count compared to placebo after a six-month regimen of high-level vitamin D supplementation [41]. The children in this study, however, had relatively preserved immunological function; mean CD4 count at study entry was 927 cells/mm3, which is a much healthier population than our study population. It is possible that any effect of vitamin D supplementation on CD4 count was masked by the high baseline values for CD4 or that supplementation is most beneficial for patients with lower baseline immunological functionality; for example, vitamin D could reduce inflammation and T cell activation, levels of which are often highest in more advanced disease. In contrast, a study of HIV-infected adults on cART with varying ranges of CD4 counts showed a positive effect of vitamin D supplementation on CD4 count [42]. Despite the high prevalence of vitamin D deficiency in HIV-positive adults, the exact relationship between vitamin D and CD4 recovery remains unclear [12]. Additional studies are ongoing and needed to further understand the role of supplementation in CD4 recovery and HIV disease progression.