African Field Epidemiology Network (AFENET) Nigeria, 50 Hallie Selassie St, Asokoro, Abuja, Nigeria; Makerere University - Johns Hopkins University Research Collaboration, Upper Mulago Hill Road, P.O. Box 23491, Kampala, Uganda There is evidence that human immunodeficiency virus (HIV) infected children have decreased bone mineral density (BMD) compared to population norms.
Makerere University - Johns Hopkins University Research Collaboration, Upper Mulago Hill Road, P.O. Box 23491, Kampala, Uganda There is evidence that human immunodeficiency virus (HIV) infected children have decreased bone mineral density (BMD) compared to population norms.
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There is evidence that human immunodeficiency virus (HIV) infected children have decreased bone mineral density (BMD) compared to population norms.1-4 Similarly, several studies have shown impaired growth among HIV infected children with several patterns of disrupted growth.5-7 Among other factors, micronutrient deficiencies are believed to contribute significantly to growth failure in HIV infected children, particularly in resource constrained settings with high background rates of micronutrient deficiencies.
HIV/AIDS RESEARCH AND TREATMENT Editorial It is Time to Explore the Potential Benefit of * *Corresponding author Routine Micronutrient Supplementation in Moreen Kamateeka, MBChB, MPH African Field Epidemiology Network (AFENET) Nigeria Optimizing Bone Health and Growth in HIV 50 Hallie Selassie Street Asokoro, Abuja, Nigeria Exposed Uninfected Children in the E-mail: mkamateeka@nfeltp.org Context of Early Antiretroviral Exposure in Volume 4 : Issue 1 Article Ref. #: 1000HARTOJ4e010 Resource Limited Settings Article History 1,2* 2 Moreen Kamateeka, MBChB, MPH ; Dorothy Sebikari, MBChB, MPH th Received: September 25th, 2017 th Accepted: September 25th, 2017 th 1African Field Epidemiology Network (AFENET) Nigeria, 50 Hallie Selassie St, Asokoro, Abuja, Published: September 26 , 2017 Nigeria 2Makerere University - Johns Hopkins University Research Collaboration, Upper Mulago Hill Citation Road, P.O. Box 23491, Kampala, Uganda Kamateeka M, Sebikari D. It is time to explore the potential benefit of rou- tine micronutrient supplementation in optimizing bone health and growth in There is evidence that human immunodeficiency virus (HIV) infected children have HIV exposed uninfected children in the 1-4 decreased bone mineral density (BMD) compared to population norms. Similarly, several context of early antiretroviral exposure studies have shown impaired growth among HIV infected children with several patterns of in resource limited settings. HIV/AIDS 5-7 disrupted growth. Among other factors, micronutrient deficiencies are believed to contribute Res Treat Open J. 2017; 4(1): e1-e4.
doi: 10.17140/HARTOJ-4-e010 significantly to growth failure in HIV infected children, particularly in resource constrained set- tings with high background rates of micronutrient deficiencies.5 Some of the major risk factors of decreased BMD in HIV infected children include antiretroviral therapy (ART) related toxic 2,8 effects particularly with tenofovir disoproxil fumarate (TDF) containing regimens.2,8 There is some evidence that micronutrient supplementation in HIV infected children improves growth and BMD. In a longitudinal study involving 37 perinatally HIV infected chil- dren done in USA, multivitamin use was independently associated with higher BMD Z-scores among multivitamin users compared to non-users.2 The provision of multiple micronutrient supplements to ART naïve HIV-infected South African children resulted in improvement in weight-for-height Z-score compared with a placebo.9 A systematic review of 11 trials mostly conducted in Africa concluded that multiple micronutrient supplements offer some clinical benefit in HIV infected children.10 These results have provided a strong rationale for the World Health Organization (WHO) recommendation for multiple micronutrient supplementation for HIV infected children, especially in settings where micronutrient deficiencies are prevalent.11 Whereas, WHO currently recommends multiple micronutrient supplementation for all HIV infected children, supplementation in HIV exposed uninfected children is recommended if they are malnourished and yet this growing population of children in resource limited settings is similarly at risk of impaired growth and bone health.12 As a result of accelerated scale-up of use of triple ARV combinations for preventing mother-to-child HIV transmission (PMTCT), worldwide, a large number of HIV exposed Uninfected (HEU) infants are exposed to triple ARVs early in life. In resource limited settings where extended breastfeeding for at least 12 months is recommended for infant survival among HIV infected women, these infants are ex- Copyright posed to ARVs (predominantly TDF and Efavirenz (EFV) containing regimens, the current ©2017 Kamateeka M. This is an WHO preferred first line triple ART combination for HIV infected pregnant women in PMTCT open access article distributed un- programmes) for up to 2 years. While lifelong ART greatly minimizes HIV transmission to der the Creative Commons Attribu- tion 4.0 International License (CC the baby, prolonged ART exposure both in utero and through extended breastfeeding raises BY 4.0), which permits unrestrict- safety concerns for the baby, including potential growth impairment and adverse effects on ed use, distribution, and reproduc- bone health. Additionally, children born to HIV infected women are already prone to under- tion in any medium, provided the nutrition related to maternal factors yet nutrition plays a critical role in bone mass formation original work is properly cited.
13,14 and mineralization during the fetal and infancy periods, Some studies have indicated lower Bone Mineral Content (BMC) and lower height-for-age Z-score (HAZ) as well as lower head circumference-for-age Z-score (HCAZ) in infants exposed to TDF 15-17 in-utero. More recently, a study that was designed to evaluate the potential bone and kidney toxic effects of TDF among HIV- infected pregnant and breastfeeding women and their infants reported that there were significant decreases in BMC among newborns whose mothers received Protease Inhibitor-based ART during pregnancy compared to those who received only zidovudine (ZDV) during pregnancy.18 Another first line antiretroviral, EFV is associated with vitamin D deficiency through multiple postulated 19,20 mechanisms. Vitamin D is critical for calcium absorption and bone mineralization and its deficiency is associated with rickets. 21-24 Therefore, EFV associated vitamin D deficiency may have potential adverse effects on bone health. The growing number of HIV infected pregnant and lactating women on TDF/EFV containing regimens for PMTCT has the potential to have a negative impact on bone health of their infants and young children. Consequently, failure to achieve adequate bone mass during early infancy may predispose these infants to increased risk of childhood fractures and osteoporosis in adulthood. Although, there is conflicting data on the effect of ART on growth in HIV exposed uninfected infants, a number of stud- ies conducted in Africa have shown that in utero ART exposure is associated with lower birth Weight for Age z-scores (WAZ) and 25,26 length for age z-score (LAZ). Coupled with high background rates of micronutrient deficiencies, prolonged ART exposure in HEU infants raises potential risk for growth impairment in this population. Given these concerns, and background rates of stunting among a third of children in many African settings, it is important to take a closer look at interventions that might counter any added negative effects on bone mineralization and growth caused by prolonged ARV exposure of up to 24-30 months during gestation and extended breast milk ingestion of ARVs among HEU children in resource limited settings.
A number of minerals including calcium, phosphorous, sodium as well as magnesium and vitamins A, B6, B12, C, D, and K, directly or indirectly affect bone mineralization.27 Several studies in both resource rich and resource limited settings have dem- onstrated some health benefit from micronutrient supplementation in children. In a blinded placebo controlled cluster randomized trial done in India involving 268 HIV uninfected children aged 6-16 years, supplementation with a micronutrient enriched beverage was associated with significantly greater increments for height, weight, whole-body bone mineral content (BMC), whole-body bone area, and BMD at the neck of the femur after 14 months in the supplemented group than in the placebo group(p<0.05).28 A recent randomized placebo controlled trial done in Tanzania revealed small but significant improvements in WAZ with zinc and multivita- min supplements among HIV unexposed infants aged 6 weeks-84 weeks.29 The growing population of HEU may benefit from early multiple micronutrient supplementation given the concerns of ef- fects of prolonged ART exposure on BMD and growth; however, to date, there is very limited published data on effect of multiple micronutrient supplementation on growth and BMC in this population. It is therefore important to evaluate the use of interventions like micronutrient supplementation in HEU infants that could potentially boost bone health and growth in this pediatric population at risk of TDF/EFV adverse drug effects, particularly in Sub-Sahara Africa where micronutrient deficiencies are prevalent. This will build on evidence that would be critical in determining the applicability of such interventions in routine care of the growing popula- tion of HEU.
CONFLICTS OF INTEREST The authors declare that they have no conflicts of interet.