P-433. Impact of Tesamorelin on Cardiovascular Disease Risk Prediction Scores in Phase 3 Studies Treatment Arms: Subanalysis
Bibliographic record
Abstract
Abstract Background The risk of cardiovascular disease (CVD) is nearly twice as high for persons with HIV (PWH) as the general population. Excess visceral abdominal fat (EVAF), the key characteristic of central adiposity, has also been associated with an increased risk of CVD in PWH. Tesamorelin, a growth hormone-releasing hormone analog, has previously demonstrated significant reductions in EVAF in two phase 3 randomized controlled trials in PWH. Yet, the impact of the reduction of EVAF from tesamorelin on CVD outcomes has been unknown. Tesamorelin Treatment Effect on CV Risk Score Methods To assess this impact, combined datasets from the phase 3 studies’ treatment arms were utilized to calculate 10-year atherosclerotic cardiovascular disease (ASCVD) risk scores at baseline and 26 weeks. A mediation analysis was conducted to characterize the significance of treatment impact via intermediate variables that factor into ASCVD risk prediction changes. Modifiable variables included systolic and diastolic blood pressure, total cholesterol (TC), high-density and low-density lipoprotein (HDL, LDL). The analysis population included 543 subjects randomized to tesamorelin treatment, 86% of which were male and 22% non-white; the median age was 47 years old. The percentage of subjects on lipid-lowering therapies, hypertension treatment, or diabetic were 46%, 37%, and 18%, respectively. Results Although the majority had low CVD risk at baseline, 44% had borderline to high CVD risk. Participants in the tesamorelin treatment arm tended toward a modest reduction in 10-year ASCVD risk prediction with estimated decrease in ASCVD risk of -0.40% (95% CI -0.89%, 0.05%). The reduction in CVD risk was relatively larger among subjects with higher CVD risk at baseline (p=0.038 for overall trend among all participants). Reductions in ASCVD risk score were driven predominantly by reductions in TC, independent of lipid lowering therapies. Conclusion In summary, this analysis provides evidence that reductions in excess visceral fat with tesamorelin lead to a significant reduction in forecasted CVD risk in PWH, resulting from reduction in TC even among a group heavily treated with lipid-lowering therapy. Given the increasing prevalence of obesity and central adiposity in PWH, more attention should be given to targeting visceral fat when considering CVD risk management. Disclosures Steven K. Grinspoon, MD, Gilead: Grant/Research Support|Kowa: Grant/Research Support|Theratechnologies: Advisor/Consultant|Viiv: Grant/Research Support Lindsay Fourman, MD, Chiesi Farmaceutici: Advisor/Consultant|Chiesi Farmaceutici: Grant/Research Support|Theratechnologies: Advisor/Consultant Takara Stanley, MD, Pfizer: Grant/Research Support Colleen McGary, PhD, Theratechnologies: Employee R Brandon Cash, PharmD, Theratechnologies: Employee
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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 | 0.025 | 0.029 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.022 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.009 | 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 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".