Our results on the association of selenium
Our results on the association of selenium deficiency and vitamin A deficiency being associated with greater CD4 recovery during treatment were surprising. As we had hypothesized a relationship in the opposite direction (deficiency being associated with lower CD4 recovery), we can only reflect on potential reasons for these observations. We would like to emphasize that our data is not necessarily suggesting that baseline deficiency in selenium or vitamin A is ‘beneficial’ in terms of CD4 recovery; instead, we hypothesize that the observed pattern in CD4 recovery may reflect a ‘catching up’ mechanism (e.g. in the setting of dhfr inhibitors resolution with cART initiation ) in individuals with baseline deficiencies, who had a lower starting CD4 count to begin with. For example, despite the increased CD4 recovery in individuals with selenium deficiency, the total CD4 counts in selenium deficient and selenium sufficient individuals were similar at week 96 (412 vs. 416, respectively); this is explained by the lower baseline CD4 counts in selenium deficient individuals. Similar ‘catching up’ also occurs in those with low BMI and baseline anemia; the results with high BMI are interesting and future studies will need to study this in greater detail. Another possible explanation for the relationship between micronutrients and CD4 recovery may be that the deficiency status itself may improve with ART, resulting in further increases in CD4 count. However, the vitamin A, but not selenium results can be explained through this reason as our previous data from this cohort showed reduction in vitamin A but not selenium deficiency after 48 weeks of cART . While studies are limited on the relationship of vitamin A deficiency and CD4 recovery, there are some studies that have examined the relationship between selenium and CD4 counts , , , . Our results appear to contradict findings from these prior studies. While there were important differences between these studies and ours based on cART status , use of supplements including multiple micronutrients , and study design , the more significant point to consider is that this relationship was observed in our analysis only after adjusting for baseline CD4 levels; in fact, a model that did not adjust for baseline CD4 levels showed that baseline selenium deficiency was associated with lower CD4 recovery (data not shown). To assess the relationship between baseline selenium deficiency and CD4 recovery, we believe that adjusting for baseline CD4 is important as it will ensure that any differences in CD4 recovery by deficiency status is not actually due to pre-existing baseline CD4 differences. Future studies should investigated whether this positive association of baseline selenium deficiency with CD4 recovery can be replicated in other populations and also whether a different type of relationship (e.g. a U-shaped relationship as seen in other studies , ) might be possible. Ongoing inflammation, as assessed by markers including CRP and sCD14, has been previously associated with HIV disease progression , , , , . In our study, high sCD14 was the only inflammation marker found to be significantly and positively associated with CD4 recovery in the multivariable model. In contrast, other studies have associated a higher sCD14 level with an increase in markers of HIV progression after cART initiation , , although these studies focused on clinical outcomes rather than CD4+ T cell recovery. Notably, similar to our results, Rajasuriar and colleagues observed faster CD4 recovery with higher baseline sCD14 levels . The authors suggested a potential biological explanation for this relationship whereby under certain circumstances, such as a high ratio of sCD14 compared to LPS-binding protein, elevated sCD14 may be protective against LPS-induced immune activation . While previous studies have shown that inflammation is not always resolved after cART , it is possible that cART impacts levels of inflammatory biomarkers. Further investigation is needed to more fully understand this relationship.