Virologic and Immunologic Response to a Boosted Double-Protease Inhibitor-Based Therapy in Highly Pretreated HIV-1-Infected Patients
Why this work is in the frame
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Bibliographic record
Abstract
PURPOSE: To assess the virologic and immunologic response to a boosted double-protease inhibitor (PI) regimen of highly pretreated patients infected with HIV-1 and to examine the role of PI resistance and concentration of serum saquinavir. METHOD: In an open-label prospective study, lopinavir/ritonavir, saquinavir-sgc, lamivudine, and other nucleoside analogues were offered to highly pretreated patients who had advanced HIV-1 infection and who had failed at least 2 previous highly active antiretroviral therapy regimens including at least 1 nonnucleoside reverse transcriptase inhibitor. The relationship between baseline drug resistance and steady-state saquinavir serum levels and early (week 4) and sustained (week 48) virologic response was documented. RESULTS: 35 advanced HIV-1 patients were enrolled. The boosted double-PI regimen was well tolerated. Twenty-two (63%) of the 35 patients had a > 0.8 log(10) decrease in HIV viral load at week 4. After 48 weeks of follow-up, the 22 patients who remained on the study therapy had an average decrease in viral load of 1 log(10) and had a median increase in CD4 cells of 60 cell/microL. Multiple logistic regression analysis indicated that genotypic resistance to both PIs and the week-3 trough concentrations of saquinavir were associated with virologic outcome at week 4. The presence of > or = 6 lopinavir mutations [odds ratio (OR) 0.03; 95% CI 0.01 to 0.79] and the 48V mutation (OR 0.01; 95%CI <0.01 to 0.88) was independently associated with lower odds of achieving an early response, whereas a higher saquinavir concentration at week 3 (OR 8.36; 95% CI 1.28 to 54.70) was associated with greater odds of an early response. CONCLUSION: These findings suggest that baseline PI resistance and saquinavir concentration were associated with virologic response and should be considered when planning salvage therapy.
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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 | 0.006 | 0.008 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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 | 0.001 |
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 it