Influence of polymorphisms within the CX3CR1 and MDR-1 genes on initial antiretroviral therapy response
Bibliographic record
Abstract
OBJECTIVE: Single nucleotide polymorphisms (SNP) in the genes encoding the human CX3CR1 chemokine receptor and the P-glycoprotein multidrug transporter have been associated with accelerated disease progression in untreated individuals and implicated in therapeutic response, respectively. This retrospective study assessed the influence of SNP in the CX3CR1 and MDR-1 genes on initial virological and immunological response in 461 HIV-infected, antiretroviral-naive individuals initiating antiretroviral therapy in British Columbia, Canada. METHODS: CX3CR1 and MDR-1 SNP were determined by PCR amplification of human DNA from plasma, followed by DNA sequencing. Time to virological success [time to HIV plasma viral load (pVL) < or = 500 copies/ml], virological failure (subsequent time to the second of two consecutive pVL > or = 500) and immunological failure (time to the second consecutive CD4 cell count below baseline) were analyzed by Kaplan-Meier methods. RESULTS: Frequencies of CX3CR1 amino acid haplotypes were 249V 280T (0.75), 249I 280M (0.15), and 249I 280T (0.1). Frequencies of MDR-1 nucleotide polymorphisms were 3435C (0.47) and 3435T (0.53). There was no effect detected for SNP in CX3CR1 or MDR-1 on time to virological success, nor of CX3CR1 and MDR-1 SNP on time to virological and immunological failure, respectively ( P > 0.1). There was a trend to earlier virological failure in the MDR-1 3435C/C genotype group ( P = 0.07), and a statistically significant trend to earlier immunological failure in individuals with the CX3CR1 249I polymorphism ( P = 0.02). These remained significant after correcting for baseline age, sex, pVL, CD4 cell count, type of therapy, and adherence ( P < or = 0.05). CONCLUSION: Polymorphisms in MDR-1 and CX3CR1 may be associated with accelerated virological and immunological therapy failure, respectively.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 | 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 | 0.000 |
| 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".