Expression of Membrane Drug Efflux Transporters in the Sigmoid Colon of HIV‐Infected and Uninfected Men
Bibliographic record
Abstract
The use of antiretroviral therapy (ART) as pre-exposure prophylaxis (PrEP) has gained global attention as a promising HIV prevention strategy in men who have sex with men. Permeability of these agents in the rectal mucosa may be partially regulated by interactions with drug efflux transporters, P-glycoprotein (P-gp), multidrug resistance-associated proteins (MRPs) and/or breast cancer resistance protein (BCRP). The objective of this work was to investigate the expression of drug efflux transporters in recto-sigmoid colon tissues of HIV-infected and uninfected men, and evaluate the association of ART and/or HIV infection with drug transporter expression. MDR1/P-gp, MRPs (1-4) and BCRP mRNA and protein expression were detected in sigmoid colon biopsies of HIV-uninfected individuals. Biopsies from HIV-infected, ART-naïve participants revealed a significant downregulation of P-gp and MRP2 protein levels compared to HIV-uninfected individuals. Biopsies from HIV-infected ART-treated patients showed 1.9-fold higher P-gp protein expression and 1.5-fold higher MRP2 protein expression compared to the ones obtained from the HIV-infected ART-naïve patients. This is a first report demonstrating that HIV infection or ART could alter expression of drug efflux transporters in gut mucosa which in turn could affect the permeability of PrEP antiretroviral agents across this barrier, a highly vulnerable site of HIV transmission.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.000 | 0.000 |
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 teacher head, 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".