HIV-1 subtype C viruses rapidly develop K65R
Bibliographic record
Abstract
The K65R substitution can cause extensive cross-resistance among currently used NRTIs, yet this mutation has rarely been observed among subtype B infected individuals who receive antiretroviral (ARV) drugs. We evaluated the incidence of K65R in subtype C patients in Botswana, who received ARV therapy in the context of first and second line regimens by studying the reverse transcriptase (RT) genotypes of 23 individuals who failed therapy, while on combination regimens that included ddI and d4T. Ten of these individuals had initiated treatment with ddI/d4T-based regimens while 13 had started therapy with ZDV/3TC/NVP or ZDV/3TC/EFV prior to switching to ddI-and/or d4T-containing combinations. Of the 23 patients, 7 possessed K65R and no-one possessed L74V after a median exposure to combination ddI/d4T of only eight months (range 4–18 months). In contrast, none of 13 patients who received 3TC/ZDV as initial therapy prior to d4T/ddI developed K65R, although most of them developed thymidine-associated mutations (TAMs); this is potentially due to antagonism between TAMs and K65R. In tissue culture studies, K65R was detected after only 12 weeks in 4/4 and 3/4 selections with Tenofovir and ddI, respectively, but far longer periods were required for relatively infrequent selection of K65R by Tenofovir with subtype B viruses (>40 weeks; 2/7 selections). K65R may emerge at higher frequency in individuals infected with subtype C viruses who experience treatment with certain NRTIs, establishing the need to monitor for the presence of this mutation and its possible 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 | 0.000 | 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) | 0.003 | 0.027 |
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; both teacher heads agree on what is shown here.
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".