Time to virologic failure for patients taking their first antiretroviral regimen and the subsequent resistance profiles
Bibliographic record
Abstract
INTRODUCTION: The resistance profiles of first-line antiretroviral therapy (ART) regimens after virologic failure have yet to be studied in a clinic setting in the modern treatment era. Time to virologic failure among three standard first-line regimens and the resistance profiles of these failures were compared. MATERIALS AND METHODS: All HIV-positive persons aged 16 and over starting a three-drug first-line ART regimen were retrospectively identified at a Toronto community clinic (1 January 2006-1 January 2013). The regimens included a backbone of two NRTIs and a third agent; a PI, an NNRTI, or an II. Patients must have been on treatment for at least 14 days and have at least one VL test within 6 months after starting treatment. The primary outcome was virologic failure defined as either: no suppression by 6 months, or after suppression, two consecutive, detectable VL200 copies/mL at least 14 days apart or one VL>200 copies/mL. Time to failure was compared using a proportional hazards model adjusting for demographic and clinical factors. Resistance profiles of NRTIs and third agents are described in patients with virologic failure who had both baseline and virologic failure genotypes. RESULTS: Six hundred sixty patients (93% male) were included with a mean age of 38.9 and a median follow-up period of 35.3 (32.2-39.3) months. Distribution of third agent use was: PI 37.3% (n=246), NNRTI 55.9% (n=369) and II 6.8% (n=45). Virologic failures occurred in 81/246 (33%) with PI, 87/369 (24%) with NNRTI and 11/45 (24%) with II. Compare to PIs, time to failure was longer with NNRTIs (p=0.0013) and similar for IIs (p=0.1562). No evidence that failure with NNRTIs was different from IIs (p=0.9139). Of the 660 patients, 567 (86%) had a baseline genotype. Of the 567 patients, 179 had virological failure. Of the 179, 145(81%) had a baseline genotype and only 37 (21%) had both a baseline and follow-up genotype. Upon failure, emerging ART resistance was rare. No new PI or II mutations were identified and one new NNRTI (Y181C) mutation was identified. Three patients taking PI-based regimens developed NRTI mutations (M184V, M184I, T215Y). CONCLUSIONS: Time to virologic failure was significantly greater in the NNRTI group compared to the PI group. If failure did occur, ART resistance rarely developed with no PI mutations but a few NRTI mutations in those taking PI-based regimens, and NNRTI mutations in those taking NNRTI-based regimen.
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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 | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 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 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".