Tenofovir: A Nucleotide Analog for The Management of Human Immunodeficiency Virus Infection
Bibliographic record
Abstract
Tenofovir disoproxil fumarate, an acyclic nucleotide analog of adenosine monophosphate, is the most recent addition to the antiretroviral arsenal. After conversion to tenofovir by diester hydrolysis, subsequent phosphorylation by cellular enzymes to form the active tenofovir diphosphate is necessary for antiretroviral activity. Preliminary data suggest that tenofovir is as safe and efficacious as stavudine when given in combination with lamivudine and efavirenz for the treatment of antiretroviral-naïve patients. In antiretroviral-experienced patients, the addition of tenofovir to stable background antiretroviral therapy resulted in approximately a 0.6 log10 copies/ml reduction in viral load relative to placebo. Extended follow-up suggests that such virologic gains may be durable. In vitro, recombinant human immunodeficiency virus (HIV) expressing the K65R mutation showed a 3-4-fold increase in the 50% inhibitory concentrations of tenofovir when compared with wild type. In vivo, this mutation thus far appears to occur infrequently and is associated with variable virologic responses. Response rates to tenofovir vary with the number and pattern of thymidine analog mutations present before starting treatment with this agent. Tenofovir appears to be a well-tolerated agent in patients who are heavily pretreated and who have advanced disease. The main adverse effects appear to be gastrointestinal in nature and include nausea, vomiting, and diarrhea. In animals, osteomalacia and nephrotoxicity have occurred with tenofovir at exposures much higher than those observed in humans. Although no patient had to discontinue therapy as a result of elevated creatinine levels or hypophosphatemia through 58 weeks of treatment, the toxicities associated with long-term tenofovir therapy in humans are unknown. Concomitant administration of tenofovir and didanosine increases the area under the concentration-time curve of the latter by 44-60%; monitoring for signs and symptoms of didanosine toxicity is recommended. The approved dosage of tenofovir is 300 mg (one tablet) once/day with meals. Given the ease of administration and relative safety from the perspectives of adverse effects and drug interactions, tenofovir has the potential to assume a large role in the treatment of patients with HIV infection.
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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 | 0.003 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".