Plasma micronutrient concentrations are altered by antiretroviral therapy and lipid-based nutrient supplements in lactating HIV-infected Malawian women

Authors: FLAX, VALERIE - University Of North Carolina; ADAIR, LINDA - University Of North Carolina; Allen, Lindsay - A; Shahab-Ferdows, Setti; HAMPEL, DANIELA - University Of California; CHASELA, CHARLES - University Of North Carolina; TEGHA, GERALD - University Of North Carolina; DAZA, ERIC - University Of North Carolina; CORBETT, AMANDA - University Of North Carolina; DAVIS, NICOLE - University Of North Carolina; KAMEWENDO, DEBORAH - University Of North Carolina; KOURTIS, ATHENA - Centers For Disease Control And Prevention (CDC) - United States; VAN DER HORST, CHARLES - University Of North Carolina; JAMIESON, DENISE - Centers For Disease Control And Prevention (CDC) - United States; BENTLEY, MARGARET - University Of North Carolina

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/5/2015
Publication Date: 7/8/2015
Citation: Flax, V.L., Adair, L.S., Allen, L.H., Shahab-Ferdows, S., Hampel, D., Chasela, C.S., Tegha, G., Daza, E.J., Corbett, A., Davis, N.L., Kamewendo, D., Kourtis, A.P., Van Der Horst, C.M., Jamieson, D.J., Bentley, M.E. 2015. Plasma micronutrient concentrations are altered by antiretroviral therapy and lipid-based nutrient supplements in lactating HIV-infected Malawian women. Journal of Nutrition. DOI: 10.3945/jn.115.212290.

Interpretive Summary: Background: Little is known about the influence of antiretroviral therapy with or without micronutrient supplementation on the micronutrient status of HIV-infected lactating women in resource-constrained settings. Objective: We examined associations of highly active antiretroviral therapy (HAART) and lipid-based (micro)nutrient supplements (LNS) with plasma concentrations of selected micronutrients in HIV-infected Malawian women at 24 wk postpartum. Methods: Plasma micronutrient concentrations were measured in a subsample (n = 690) of Breastfeeding, Antiretrovirals, and Nutrition (BAN) study participants who were randomly assigned at delivery to receive HAART, LNS, HAART+LNS, or no HAART/no LNS (control). HAART consisted of protease inhibitor–based triple therapy. LNS (140 g/d) met the mothers’ energy and micronutrient requirements for lactation. Multivariable linear regression tested the association of HAART and LNS, plus their interaction, with micronutrient concentrations, controlling for season, baseline viral load, and baseline CD4 count. Results: We found significant HAART by LNS interactions for plasma folate (P = 0.051), vitamin B-12 (P < 0.001), and transferrin receptors (TfRs) (P = 0.085). HAART (compared to the no HAART group) was associated with lower folate (with LNS: -27%, P < 0.001; without LNS: -12%, P = 0.040) and higher TfR concentrations (with LNS: +14%, P = 0.004; without LNS: +28%, P < 0.001), indicating iron deficiency. LNS (compared to no LNS) increased plasma folate (with HAART: +17%, P = 0.037; without HAART: +39%, P < 0.001) and decreased TfR concentrations (with HAART only: 212%, P = 0.023). HAART was associated with lower plasma vitamin B-12 concentrations only when LNS was provided (-18%, P = 0.001), whereas LNS increased vitamin B-12 only when no HAART was provided (+27%, P < 0.001). HAART, but not LNS, was associated with higher retinol-binding protein (RBP; +10%, P = 0.007). We detected no association of HAART or LNS with plasma selenium or ferritin, or hemoglobin. Conclusion: The association of HAART with lower plasma folate, iron deficiency, and higher RBP, and the attenuated LNS effects on plasma folate and vitamin B-12 when combined with HAART has implications for the health of lactating HIV-infected women taking HAART in prevention of mother-to-child transmission programs. This trial was registered at clinicaltrials.gov as NCT00164736.

Technical Abstract: Methods: Plasma micronutrient concentrations were measured in a subsample (n = 690) of Breastfeeding, Antiretrovirals, and Nutrition (BAN) study participants who were randomly assigned at delivery to receive HAART, LNS, HAART+LNS, or no HAART/no LNS (control). HAART consisted of protease inhibitor–based triple therapy. LNS (140 g/d) met energy and micronutrient requirements of lactation. Multivariable linear regression tested the association of HAART and LNS, plus their interaction, with micronutrient concentrations, controlling for season, baseline viral load, and baseline CD4 count. Results: We found significant HAART by LNS interactions for folate (P = 0.051), vitamin B-12 (P < 0.001), and transferrin receptors (TfRs) (P = 0.085). HAART was associated with lower folate (with LNS: -27%, P < 0.001; without LNS: -12%, P = 0.040) and higher TfR concentrations (with LNS: +14%, P = 0.004; without LNS: +28%, P < 0.001), indicating iron deficiency. LNS increased folate (with HAART: +17%, P = 0.037; without HAART: +39%, P < 0.001) and decreased TfR concentrations (with HAART only: -12%, P = 0.023). HAART was associated with lower vitamin B-12 concentrations only when LNS was present (-18%, P = 0.001), whereas LNS increased vitamin B-12 only when no HAART was present (+27%, P < 0.001). HAART, but not LNS, was associated with higher retinol-binding protein (RBP; +10%, P = 0.007). We detected no association of HAART or LNS with selenium, ferritin, or hemoglobin. Conclusion: The association of HAART with lower folate, iron deficiency, and higher RBP plus the attenuation of LNS effects on folate and vitamin B-12 when combined with HAART has implications for the health of lactating HIV-infected women taking HAART in prevention of mother-to-child transmission programs. This trial was registered at clinicaltrials.gov as NCT00164736.