Prevalence and risk factors of micronutrient deficiencies pre- and post-antiretroviral therapy (ART) among a diverse multicountry cohort of HIV-infected adults

Abstract

Background & aims: HIV-infected adults have increased risk of several individual micronutrient deficiencies. However, the prevalence and risk factors of concurrent and multiple micronutrient deficiencies and whether micronutrient concentrations change after antiretroviral therapy (ART) initiation have not been well described. The objective of this study was to determine the prevalence and risk factors of individual, concurrent and multiple micronutrient deficiencies among ART-naïve HIV-infected adults from nine countries and assess change in micronutrient status 48 weeks post-ART initiation.

Methods: A random sub-cohort (n = 270) stratified by country was selected from the multinational PEARLS clinical trial (n = 1571 ART-naïve, HIV-infected adults). We measured serum concentrations of vitamins A, D (25-hydroxyvitamin), E, carotenoids and selenium pre-ART and 48 weeks post-ART initiation, and measured vitamins B6, B12, ferritin and soluble transferrin receptor at baseline only. Prevalence of single micronutrient deficiencies, concurrent (2 coexisting) or conditional (a deficiency in one micronutrient given a deficiency in another) and multiple (≥3) were determined using defined serum concentration cutoffs. We assessed mean changes in micronutrient concentrations from pre-ART to week 48 post-ART initiation using multivariable random effects models.

Results: Of 270 participants, 13.9%, 29.2%, 24.5% and 32.4% had 0, 1, 2 and multiple deficiencies, respectively. Pre-ART prevalence was the highest for single deficiencies of selenium (53.2%), vitamin D (42.4%), and B6 (37.3%) with 12.1% having concurrent deficiencies of all three micronutrients. Deficiency prevalence varied widely by country. 48 weeks post-ART initiation, mean vitamin A concentration increased (p < 0.001) corresponding to a 9% decrease in deficiency. Mean concentrations also increased for other micronutrients assessed 48 weeks post-ART (p < 0.001) but with minimal change in deficiency status.

Conclusions: Single and multiple micronutrient deficiencies are common among HIV-infected adults pre-ART initiation but vary between countries. Importantly, despite increases in micronutrient concentrations, prevalence of individual deficiencies remains largely unchanged after 48 weeks on ART. Our results suggest that ART alone is not sufficient to improve micronutrient deficiency.

Keywords: Antiretroviral therapy; Cohort studies; HIV; Micronutrient deficiency; Multiple micronutrients; Vitamins.

Conflict of interest statement

Conflict of Interest

All authors declare no conflicts of interest.

Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Figures

Figure 1. Pre-ART initiation micronutrient concentrations and prevalence of individual deficiencies in HIV-infected adults

Number (n), median and the interquartile range (IQR), and the prevalence of deficiency (%) and 95% confidence interval (CI) is presented for vitamin A (A), total carotenoids (Car), vitamin B12 (B12), vitamin B6 (B6), vitamin E (E), iron and slenium (Sel) measured pre-ART initiation. The total sample size (n) varies due to insufficient serum for analysis or missing data. Cutoff values for deficiency include: <1.05 μmol/L for retinol (vitamin A), <19 nmol/L for vitamin B6, <148 pmol/L for vitamin B12, <9.3 μmol/L for α-tocopherol (vitamin E) and <85 μg/L for selenium. Iron deficiency (ID) was defined by either transferrin receptor concentration (> 8.3 mg/L) or ferritin concentration (ferritin < 12 μg/L if CRP ≤5 mg/L or ferritin < 30 μg/L if CRP >5 mg/L).

Figure 2. Risk factors for individual and multiple micronutrient deficiencies pre-ART initiation

Independent risk factors for vitamin A, B6, B12 and multiple (≥3 concurrent deficiencies) micronutrient deficiencies. Odds ratio (■) with 95% confidence intervals (CI) are shown only for variables with significant (based on CI) odds of deficiency in multivariable logistic regression models adjusting for gender, country, BMI, CD4 count, log viral load and CRP. Multiple micronutrient deficiencies were defined as deficiency in three or more micronutrients when considering vitamins A, B6, B12, D, E, selenium, iron and low total carotenoids. High CRP is defined as CRP levels ≥5 mg/L with low CRP as the reference group. Low body mass index (BMI) is defined as BMI <18.5 kg/m2 with normal BMI (18.5–25 kg/m2) as the reference group. CD4 categories with counts of 200–300 cells/mm3 were the reference group for CD4 count and viral load categories with log viral load less than 4 copies/mL were the reference group for viral load. For vitamin A, B6, B12 and multiple deficiencies, the reference countries were Thailand, South Africa, Peru and Haiti, respectively. The country with the lowest non-zero prevalence of deficiency was chosen as the reference country for each micronutrient. Deficiencies are based on cutoffs used in Table 1.