Bictegravir decreases expression of system L-amino acid transporters and inhibits leucine uptake activity in a human placental cell line
Bibliographic record
Abstract
Antiretroviral therapy (ART) improves maternal health and reduces perinatal HIV transmission; however, it has been associated with increased risk for adverse outcomes via mechanisms that are poorly understood. Branched-chain amino acids (BCAAs) are important for fetal development and cardiometabolic health. Alterations in BCAAs have been reported in pregnant people with HIV and children exposed to ART in utero . System L-amino acid transporters are key in transporting BCAAs across the placenta, but their functionality in the context of ART use has not been investigated. Here we examine the effects of antiretrovirals on the expression and function of system L transporters. Syncytialized BeWo cells were treated with atazanavir, darunavir, efavirenz, dolutegravir, raltegravir, bictegravir or cabotegravir for 24 h at C max and half C max therapeutic concentrations. Cytoplasmic and membrane protein expression of system L isoforms were quantified by western blot. System L transport activity was measured using [ 3 H]-tritium-labelled L-leucine uptake assays in the presence or absence of a system L-specific inhibitor. System L isoforms LAT-1 and LAT-2 were primarily expressed in the plasma membrane, whereas LAT-4 expression was predominantly cytoplasmic. Bictegravir significantly reduced the protein levels of all 3 isoforms. Cabotegravir was associated with lower LAT-1 and LAT-4 and efavirenz with lower LAT-1 and LAT-2 levels. A reduction in leucine transport was only observed with bictegravir treatment. Bictegravir, which has been recently added to perinatal treatment guidelines, was associated with downregulation of system L expression and function in BeWo cells. Further in vivo studies are warranted to confirm our findings.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".