Antiretroviral Treatment Is Associated With Iron Deficiency in HIV-Infected Malawian Women That Is Mitigated With Supplementation, but Is Not Associated With Infant Iron Deficiency During 24 Weeks of Exclusive Breastfeeding.
OBJECTIVE
In resource-limited settings without safe alternatives to breastfeeding, the WHO recommends exclusive breastfeeding and antiretroviral (ARV) prophylaxis. Given the high prevalence of anemia among HIV-infected women, mothers and their infants (through fetal iron accretion) may be at risk of iron deficiency. We assessed the effects of maternal micronutrient-fortified lipid-based nutrient supplements (LNS) and maternal ARV treatment or infant ARV prophylaxis on maternal and infant iron status during exclusive breastfeeding from birth to 24 weeks.


METHODS
The Breastfeeding, Antiretrovirals, and Nutrition study was a randomized controlled trial conducted in Lilongwe, Malawi, from 2004 to 2010. HIV-infected mothers (CD4 >200 cells/μL) and their infants were randomly assigned to 28-week interventions: maternal LNS/maternal ARV (n = 424), maternal LNS/infant ARV (n = 426), maternal LNS (n = 334), maternal ARV (n = 425), infant ARV (n = 426), or control (n = 334). Longitudinal models tested intervention effects on hemoglobin (Hb). In a subsample (n = 537) with multiple iron indicators, intervention effects on Hb, transferrin receptors (TfR), and ferritin were tested with linear and Poisson regression.


RESULTS
In longitudinal models, LNS effects on maternal and infant Hb were minimal. In subsample mothers, maternal ARVs were associated with tissue iron depletion (TfR >8.3 mg/L) (risk ratio: 3.1, P < 0.01), but not in ARV-treated mothers receiving LNS (P = 0.17). LNS without ARVs was not associated with iron deficiency or anemia (P > 0.1). In subsample infants, interventions were not associated with impaired iron status (all P > 0.1).


CONCLUSIONS
Maternal ARV treatment with protease inhibitors is associated with maternal tissue iron depletion; but LNS mitigates adverse effects. ARVs do not seem to influence infant iron status; however, extended use needs to be evaluated.
*Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC; †Department of Nutrition, University of Witwatersrand, Parktown, South Africa; ‡Faculty of Health Sciences,UNC Project, Lilongwe, Malawi; §Division of Reproductive Health, US Centers for Disease Control and Prevention, Atlanta, GA; and #US Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center, Davis, CA.
Elizabeth M
EM
Widen
Margaret E
ME
Bentley
Charles S
CS
Chasela
Dumbani
D
Kayira
Valerie L
VL
Flax
Athena P
AP
Kourtis
Sascha R
SR
Ellington
Zebrone
Z
Kacheche
Gerald
G
Tegha
Denise J
DJ
Jamieson
Charles M
CM
van der Horst
Lindsay H
LH
Allen
Setareh
S
Shahab-Ferdows
Linda S
LS
Adair
D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001942:Breast Feeding; D019587:Dietary Supplements; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007501:Iron / Q000008:administration & dosage / Q000627:therapeutic use; D000090463:Iron Deficiencies; D019266:Iron, Dietary / Q000008:administration & dosage / Q000494:pharmacology; D008137:Longitudinal Studies; D008295:Malawi / Q000453:epidemiology; D008297:Male
D019380:Anti-HIV Agents; D006454:Hemoglobins; D019266:Iron, Dietary; D007501:Iron