Retroviral Biodiversity: Practical Consequences for HIV Treatment and Prevention
Bibliographic record
Abstract
Background: Retroviral diversity is attributable both to the infidelity of the reverse transcriptase (RT)enzyme that is responsible for transcribing the viral RNA genome into DNA as well as to a high viral replication rate. In the case of HIV-1, the error rate of RT is approximately 5 × 10−5. Given a genomic length of 9.2 kb, this means that a mutation is likely to take place almost every time that HIV replicates; consequently, mutations are found throughout the HIV genome infected individuals. These mutations include those responsible for escape from immunological pressure as well as those associated with drug resistance. HIV replication patterns in different areas of the world have also given rise to a series of subtypes and recombinant forms that predominate in different geographic locales. Proper interpretation of drug resistance mutational patterns has potentiated both the sequencing of drugs within a given drug class, as well as the use of drugs from classes that have not previously been used in treatment of a given patient. Drug resistance is today acknowledged to be both a key cause as well as outcome of HIV treatment failure. Results: In recent years, however, the field of HIV resistance testing has become complicated by the fact that different viral subtypes may sometimes express different mutations that are associated with resistance to the same compound. In some cases, this may be due to the redundancy of the genetic code and the fact that different viral subtypes may employ different codons in order to express the same amino acid. An example of this is the V106M mutation that encodes resistance against NNRTIs in subtype C viruses, as opposed to V106A in subtype B. In other instances, viral RNA template sequences may vary between subtypes such that certain mutations are preferentially selected under drug pressure. As an example, subtype C viruses seem more prone to develop the K65R mutation that causes broad cross-resistance to a range of nucleoside compounds, whereas this mutation is very rare in subtype B viruses. Conclusions: These findings have relevance for both treatment and prevention strategies in countries in which subtype C viruses are predominant.
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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 | 0.006 | 0.008 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.006 |
| Scholarly communication | 0.004 | 0.006 |
| Open science | 0.001 | 0.003 |
| Research integrity | 0.004 | 0.005 |
| Insufficient payload (model declined to judge) | 0.022 | 0.004 |
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".