Although 25(OH) D levels are commonly used to define vitamin D status, its suitability and applicability as a predictor for good prognosis in children on HIV care remains debatable. In our study, we examined the relationship between age categories and levels of vitamin D. Our results revealed that levels of vitamin D in children increases with increasing age during1-4 years to reach peak levels of 31.91ng/ml and begin to decline (Fig. 1). Supposedly, this value represents the physiologically ideal level of vitamin D much required to optimize various vitamin D high level viremia-associated health outcomes and physiological parameters such as bone mineral density [17]; and is perfectly comparable with 36.5ng/ml peak levels at 18 month postnatal earlier reported in a Malawi study [18], Furthermore, our finding is supported by Mogire et al [19] and Alvarez-Rodriguez et al [20] who equally observed a decreasing trend with vitamin D levels as age increases; and associated the same with a change in expression and defective function of some toll-like receptors (TLRs) involved in viral response [20]. To the contrary, a similar study among HIV uninfected infants in our neighborhood Tanzania observed that low levels of vitamin D was common in infants during their early infancy, especially those under exclusive breastfeeding.[21], the cause of which remain unclear.
Furthermore, we compared the mean levels of vitamin D between HIV infected and uninfected children receiving antiretroviral therapy (ART) with those on routine outpatient visits. Our data analysis revealed that HIV infected children profoundly experienced low levels of vitamin D as compared to their uninfected counterparts. Interestingly, this is explained by the fact that persons living with HIV (PLWH), and receiving ART particularly protease inhibitor (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) traditionally experience suppressed levels of vitamin D in blood [22], but which becomes more exacerbated in individuals receiving efavirenz (EFV) [5, 23]; the mechanism of which is under investigation. Moreover, much lower levels of serum vitamin D have equally been observed among late ART-initiated children (18 months to 12 years) as compared to those on early-ART initiation in the first year of life [22], but this is explained by the influence of increasing age on vitamin D levels reported in our study; and is consistent with children physiological parameters such as bone mineral density [17].Thus, our finding supported an earlier systematic review and meta-analysis report showing increased risk of vitamin D deficiency in PLWH compared to uninfected subjects; more so to participants receiving ART, and in older age category [24]. Slightly lower levels of vitamin D among HIV infected infants and adults on ART have equally been reported in a similar study in Botswana [4], although this was partly attributed to demographic and dietary habits of consuming more of traditional and indigenous foods enriched with better dietary diversity [4]
Additionally, we compared the proportion of Immunocompromised participants with Immunocompetent group based on their vitamin D levels, and established that majority participants who experienced vitamin D deficiency or insufficiency were actually Immunocompetent rather than Immunocompromised; and consistent with earlier findings by Kakalia et al, [25]. To the contrary, our findings dispelled earlier report suggesting a possible correlation between vitamin D levels and CD4 + T-cell counts [3, 5, 26]. Instead, vitamin D concentrations above 30 ng/ml has been found to be more associated with mortality of HIV infected children compared to levels lower than 10 ng/ml [21]. Meanwhile, a good number of local and international studies have reported varying relationship; both positive and negative, with others failing to demonstrate any correlation [27] A recent study in the neighborhood Uganda associated low CD4 count with vitamin D deficiency [5]; thus, echoing other findings from related studies in France and Colombia which equally suggested that severe vitamin D deficiency could be independently associated with low CD4 count [3, 4, 28]. Although high CD4 cells counts have been associated with higher vitamin D levels [29], while low vitamin D levels is linked to immune dysfunction that also influence the expression of inflammatory markers [24], we could not establish this outcome owing to the scope of our study. Moreover, it is good to note that children in our study had been on ART for quite some times, majority of whom were experiencing good health status by the time of sampling; hence, the immunologic, HIV stage and other HIV related factors may have normalized and compensated for the effects of vitamin D status. We however still believe that this could have been a bit different in children who may have had advanced disease at ART initiation.
Moreover, we compared the proportions of participants who achieved optimal viral suppression visa-vi those with sub optimal suppression and their levels of vitamin D; and found that those who were optimally suppressed were in fact the majority with either vitamin D deficiency or insufficiency contrary to earlier suggestion by Stalling et al that vitamin D supplementation intervention to sufficient levels helps to improve viral suppression of patients on ART[13] Our findings equally dispute earlier suggestion by Overton et al that high dose supplementation of vitamin D with ART substantially enhance viral suppression [30].
This study included a number of limitations. First, the small sample size and single site experience limits generalizability and requires further study in multisite samples. Additionally, our study was performed entirely in Kisumu western Kenya, an equatorial region abundant with sunshine which may have compensated for deficiency attributed to diet or HIV infection; thus, generalizability to other regions with less sunshine may be limited. Finally, our population consisted of children with relatively preserved immune function, having been on ART for sometimes and therefore our failure to accurately demonstrate the relationship between vitamin D status, CD4 count and viral load; hence, cannot be generalized to children with more advanced HIV disease and low baseline CD4 counts.