ReviewSelenium supplementation in HIV-infected individuals: A systematic review of randomized controlled trials
Introduction
Despite significant advances in HIV-antiretroviral therapy, the HIV epidemic remains a significant health problem, and no definitive cure is in sight [1]. In 2017, an estimated 36.9 (31.1–43.9) million people were living with HIV worldwide [2]. However, only 47% of those living with HIV were virally suppressed as of July 2017 [3]. People living with HIV (PLWH) have an elevated risk of malnutrition [4]. In addition, micronutrient deficiencies, including selenium, are known to be prevalent during HIV-infection with significant effects on the immune system [5] and antioxidant defense [6]. Micronutrient deficiencies weaken immunity, thus can promote the progression of HIV-infection to AIDS. HIV-infection, in turn, aggravates micronutrient deficiencies, leading to a vicious circle.
Selenium (Se) is required for the biosynthesis of selenoenzymes, such as glutathione peroxidase, as it is incorporated into those proteins in the form of selenocysteine (Sec). Selenoenzymes protect against oxidative stress and activate thyroid hormones. Nonetheless, selenium is toxic if ingested in excessive amounts [7]. It is a micronutrient having potent antioxidant and anti-inflammatory functions mediated through selenoproteins [8]. Although selenium intake may benefit individuals with low selenium status, many of its biological and clinical benefits are relatively unknown to some clinicians [9]. Selenium supplementation is beneficial to PLWH [10]. The rationale for using selenium supplementation in HIV-infected persons stems from the hypothesis that selenium is a key micronutrient to maintain a responsive immune system [10] along with its potential to prevent HIV replication [11]. Furthermore, low selenium status is thought to be linked to a high risk of tuberculosis [12] and mortality [13], [14] in HIV/AIDS patients.
However, selenium is not yet widely recommended in routine care in individuals infected with HIV. Some of the reluctance among clinicians to recommend selenium supplements is a result of a lack of clinical evidence and data, and our limited understanding about selenium supplementation in HIV-infected patients. Concerns have also been raised about high selenium status in HIV-1 infected adults being associated with clinical failure [5] and risk of increased HIV infectivity in women [15]. Randomized controlled trials (RCT) that have assessed the effects of selenium supplementation in PLWH have yielded heterogeneous results [16], [17]. In 2007, daily selenium supplementation of 200 μg was reported to suppress HIV in American adults [11]. However, in 2015, findings from a Rwandan study using the same dose (200 μg) of selenium in HIV-infected adults failed to support the hypothesis that selenium can suppress HIV [18]. However, the authors recognized that selenium can improve the rate of cluster of differentiation 4 (CD4) count [18].
Using evidence from RCTs, we carried out this systematic review in an effort to find an answer to the following question: Does daily selenium supplementation in HIV-infected persons delay HIV-infection progression?
Section snippets
Study design and literature search
A systematic review was undertaken in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines [19]. We conducted a systematic review of clinical trials in HIV-infected adults, with or without antiretroviral therapy, randomized to receive selenium supplementation or placebo. We conducted our literature search in the Excerpta Medica Database (EMBASE) and Medline (Between January 2000 and June 2018), using the following search terms: (‘Human
Search
We retrieved 507 studies from our search (Fig. 1). Of these, 9 trials were potentially eligible [11], [15], [18], [21], [22], [23], [24], [25], [26]. Further screening eliminated three of these studies as they were deemed less relevant to our research question [15], [25], [26]. In the end, six RCTs evaluating the efficacy of selenium supplementation in adults infected with HIV were included in this review [11], [18], [21], [22], [23], [24].
Study characteristics
Characteristics of the included RCTs are presented in
Discussion
In this review, the efficacy of selenium to delay the progression of HIV-infection was assessed. Six placebo-controlled RCTs were included. Overall, data from the reviewed RCTs suggest that supplementation with daily selenium (200 μg) among either ART-naïve HIV-infected patients or those receiving ART/HAART does not suppress HIV, but can delay the decrease in CD4 cell count and thus prolong the onset of AIDS.
However, like in other studies [16], [17], we found that definitive conclusions cannot
Conclusion
We did not find any quantifiable evidence that selenium supplementation suppresses HIV but the reviewed studies show that selenium can delay the decline in CD4 in specific patients infected with HIV. However, we are unable to arrive at any definitive conclusions at this stage. The question about whether “daily selenium supplementation in HIV-infected persons delays HIV-infection progression to AIDS” still needs further investigation in adequately-performed and analyzed RCTs that assess the
Contributors
BAM and NRN were responsible for the design, data collection, and data synthesis. BAM wrote the first draft of the manuscript. NRN, KJ, HLH, CN, TS, KW and SI revised and edited the manuscript.
Funding
“This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.”
Declaration of interests
None to declare.
Acknowledgements
The authors would like to thank Mr. Matthew McLaughlin from the International University of Health and Welfare and Mrs. Mansongi Biyela Carine for their helpful suggestions through the preparation and composition of this manuscript.
References (37)
- et al.
Advancing global health and strengthening the HIV response in the era of the sustainable development goals: the international AIDS society-lancet commission
Lancet
(2018) Selenium and human health
Lancet
(2012)- et al.
Selenium and exposure to fibrogenic mineral dust: a mini-review
Environ Int
(2015) - et al.
Selenium status is associated with accelerated HIV disease progression among HIV-1-infected pregnant women in Tanzania
J Nutr
(2004) The importance of selenium to human health
Lancet
(2000)- et al.
Randomized, double-blind, placebo-controlled trial of selenium supplements among HIV-infected pregnant women in Tanzania: effects on maternal and child outcomes
Am J Clin Nutr
(2008) - et al.
Plasma and breast-milk selenium in HIV-infected Malawian mothers are positively associated with infant selenium status but are not associated with maternal supplementation: results of the Breastfeeding, Antiretrovirals, and Nutrition study
Am J Clin Nutr
(2014) - et al.
Selenium supplementation in HIV-infected patients: is there any potential clinical benefit?
J Assoc Nurses AIDS Care
(2009) - et al.
Glutathione, glutathione peroxidase, and selenium status in HIV-positive and HIV-negative adolescents and young adults
Am J Clin Nutr
(2007) - et al.
Dietary selenium in adjuvant therapy of viral and bacterial infections
Adv Nutr
(2015)