Metabolomics in Placental Tissue from Women Living with HIV.

MedStar author(s):
Citation: AIDS Research & Human Retroviruses. 38(3):198-207, 2022 03.PMID: 34498948Institution: MedStar Health Research Institute | MedStar Washington Hospital CenterDepartment: Obstetrics and Gynecology/Maternal-Fetal MedicineForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: *Anti-HIV Agents | *HIV Infections | Anti-HIV Agents/ae [Adverse Effects] | Anti-HIV Agents/me [Metabolism] | Anti-Retroviral Agents/tu [Therapeutic Use] | Female | HIV Infections/dt [Drug Therapy] | HIV Infections/me [Metabolism] | Humans | Infant, Newborn | Metabolomics | Placenta/me [Metabolism] | PregnancyYear: 2022ISSN:
  • 0889-2229
Name of journal: AIDS research and human retrovirusesAbstract: It is unknown whether antiretroviral (ARV) drugs in women living with HIV (WLHIV) are associated with mitochondrial toxicity and altered fat oxidation and branched-chain amino acid metabolism in the placenta and fetus. Immediately after delivery, we froze placental biopsies from 20 WLHIV and 20 matched uninfected women. We analyzed global biochemical profiles using high-performance liquid chromatography/tandem mass spectrometry and gas chromatography/mass spectrometry. We used t-tests, principle component analysis, hierarchical clustering, and random forest analysis (RFA) in our analysis. Twelve WLHIV were on protease inhibitors, six on non-nucleoside reverse inhibitors, and two on integrase strand inhibitors with optimized backbone. Mean birth weight of HIV-exposed neonates was significantly lower than unexposed neonates (3,075 g vs. 3,498 g, p = .01) at similar gestational age. RFA identified 30 of 702 analytes that differentiated the placental profiles of WLHIV from uninfected women with 72.5% predictive accuracy. Placental profiles of non-nucleoside reverse transcriptase inhibitor (NNRTI)-treated WLHIV exhibited lower levels of amino acids, including essential and branched-chain amino acids, and some medium-chain acylcarnitines. Placental metabolism may be altered in WLHIV, possibly associated with ARV exposure. The lower birth weight among neonates of WLHIV suggests the need for further studies considering potential deleterious effects of altered placenta metabolism on fetal growth and development.All authors: Al-Kouatly HB, Cunningham G, Inagaki K, Ingram BO, Kirmse B, Makhamreh MM, Rakhmanina N, Scott RK, Visclosky TOriginally published: AIDS Research & Human Retroviruses. 2021 Dec 13Fiscal year: FY2022Digital Object Identifier: ORCID: Date added to catalog: 2021-11-01
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Journal Article MedStar Authors Catalog Article 34498948 Available 34498948

It is unknown whether antiretroviral (ARV) drugs in women living with HIV (WLHIV) are associated with mitochondrial toxicity and altered fat oxidation and branched-chain amino acid metabolism in the placenta and fetus. Immediately after delivery, we froze placental biopsies from 20 WLHIV and 20 matched uninfected women. We analyzed global biochemical profiles using high-performance liquid chromatography/tandem mass spectrometry and gas chromatography/mass spectrometry. We used t-tests, principle component analysis, hierarchical clustering, and random forest analysis (RFA) in our analysis. Twelve WLHIV were on protease inhibitors, six on non-nucleoside reverse inhibitors, and two on integrase strand inhibitors with optimized backbone. Mean birth weight of HIV-exposed neonates was significantly lower than unexposed neonates (3,075 g vs. 3,498 g, p = .01) at similar gestational age. RFA identified 30 of 702 analytes that differentiated the placental profiles of WLHIV from uninfected women with 72.5% predictive accuracy. Placental profiles of non-nucleoside reverse transcriptase inhibitor (NNRTI)-treated WLHIV exhibited lower levels of amino acids, including essential and branched-chain amino acids, and some medium-chain acylcarnitines. Placental metabolism may be altered in WLHIV, possibly associated with ARV exposure. The lower birth weight among neonates of WLHIV suggests the need for further studies considering potential deleterious effects of altered placenta metabolism on fetal growth and development.

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