BackgroundHIV, cancer, and their respective treatments are independently associated with cardiovascular risk, but limited data exist on the intersection of these conditions. The purpose of this study was to gain insights into the cardiovascular risk factor burden and cardiac function in people with HIV (PWH) treated for breast cancer.MethodsIn a cohort of PWH and breast cancer treated with anthracyclines and/or trastuzumab (2017–2022) in Botswana, we assessed pre-treatment (baseline) left ventricular ejection fraction (LVEF), and prospectively obtained an echocardiogram at least one year after cancer treatment initiation. Wilcoxon signed rank sum test was used to test the differences between baseline and follow-up LVEF.ResultsThirty-three women were enrolled at a median of 2.1 years (Quartile (Q)1-Q3 1.8–3.1) from their cancer treatment initiation. The median age was 48.0 years (Q1-Q3 44.0–54.0). All but one patient was on antiretroviral therapy (ART); the median ART duration was 11.6 years (Q1-Q3 6.3–15 years) with a median viral load of 30 (Q1-Q3 0–30) and CD4 count of 874 (Q1-Q3 361–1131). At baseline, 70% were obese or overweight, and 24.2% reported hypertension; this increased to 30.3% at follow-up. The median LVEF at baseline was 65% (Q1-Q3 60–68%), and decreased to 62% (Q1-Q3 59–65%) at follow-up; an absolute difference of 2.9%, 95%CI: -5.3 to -0.2% (p = 0.038). There was no report of clinical heart failure.ConclusionsObesity and hypertension are highly prevalent amongst PWH and breast cancer. We also noted a statistically significant, but modest decline in LVEF after cancer therapy initiation. Further studies are needed to prospectively characterize the cardiovascular risk factor burden and changes in cardiac structure and function following cardiotoxic cancer treatment in this population.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40959-025-00417-3.

IntroductionAnthracycline-induced cardiotoxicity (AIC) is a serious complication of chemotherapy, and there is a need for cost-effective biomarkers to enable risk stratification. Serum neprilysin (sNEP) has been investigated as a biomarker in various cardiovascular conditions, but its role in AIC has not been evaluated.MethodsTwelve-week-old Sprague–Dawley rats received intraperitoneal doxorubicin (DOX) either as a single 20 mg/kg dose (acute model, n = 8), four weekly doses of 5 mg/kg (chronic model, n = 11), or saline (controls, n = 8 for each model). Echocardiography was performed at baseline and on the final study day. Blood and left ventricular (LV) tissue were collected within 24 h (acute model) or one week (chronic model) after the last injection. NEP protein and mRNA expression were measured in LV tissue, and sNEP concentrations were determined in serum.ResultsIn the chronic AIC model, LV NEP protein expression was significantly reduced compared with controls (982.56 ± 90.57 vs. 1132.86 ± 132.30 ng/L, p < 0.05). In the acute model, sNEP levels showed a strong positive correlation with the severity of LV cardiomyocyte vacuolization (rs = 0.81, p < 0.05). In the chronic model, sNEP levels were strongly and negatively correlated with cardiac output (r = − 0.91, p < 0.05).ConclusionsChronic DOX exposure reduces LV NEP protein expression. Elevated serum sNEP is associated with greater early cardiomyocyte injury, while in chronic AIC, it correlates with a more severe decline in cardiac output. These findings suggest sNEP may be a potential biomarker for AIC.

In cardio-oncology, the gap between mechanistic studies and pharmacological trials impedes the delineation of effective cardioprotective strategies. The angiotensin-receptor/neprilysin inhibitor (ARNI) have shown beneficial effects in patients with heart failure with reduced ejection fraction, but failed to show significant benefit in cardio-oncology. In a preclinical model, soluble neprilysin levels (sNEP) tracked anthracycline-induced myocardial damage and systolic dysfunction and sNEP levels may predict benefits of ARNI. The neutral results of clinical trials testing sacubitril/valsartan in this setting underscore the challenge of bridging pre-clinical knowledge to patients’ management and call for clinical trials in precision medicine approaches in which biomarkers (i.e. sNEP) may guide treatment (i.e. ARNI).