Risk factors for clonal hematopoiesis of indeterminate potential in people with HIV: a report from the REPRIEVE trial.

ABSTRACT: Clonal hematopoiesis of indeterminate potential (CHIP), the clonal expansion of myeloid cells with leukemogenic mutations, results in increased coronary artery disease (CAD) risk. CHIP is more prevalent among people with HIV (PWH), but the risk factors are unknown. CHIP was identified among PWH in REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) using whole-exome sequencing. Logistic regression was used to associate sociodemographic factors and HIV-specific factors with CHIP adjusting for age, sex, and smoking status. In the studied global cohort of 4486 PWH, mean age was 49.9 (standard deviation [SD], 6.4) years; 1650 (36.8%) were female; and 3418 (76.2%) were non-White. CHIP was identified in 223 of 4486 (4.97%) and in 38 of 373 (10.2%) among those aged ≥60 years. Age (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.05-1.09; P < .0001) and smoking (OR, 1.37; 95% CI, 1.14-1.66; P < .001) associated with increased odds of CHIP. Globally, participants outside of North America had lower odds of CHIP including sub-Saharan Africa (OR, 0.57; 95% CI, 0.4-0.81; P = .0019), South Asia (OR, 0.45; 95% CI, 0.23-0.80; P = .01), and Latin America/Caribbean (OR, 0.56; 95% CI, 0.34-0.87; P = .014). Hispanic/Latino ethnicity (OR, 0.38; 95% CI, 0.23-0.54; P = .002) associated with significantly lower odds of CHIP. Among HIV-specific factors, CD4 nadir <50 cells/mm3 associated with a 1.9-fold (95%CI, 1.21-3.05; P = .006) increased odds of CHIP, with the effect being significantly stronger among individuals with short duration of antiretroviral therapy (ART; OR, 4.15; 95% CI, 1.51-11.1; P = .005) (Pinteraction= .0492). Among PWH at low-to-moderate CAD risk on stable ART, smoking, CD4 nadir, North American origin, and non-Hispanic ethnicity associated with increased odds of CHIP. This trial was registered at www.ClinicalTrials.gov as NCT02344290.

Randomized trial comparing dose reduction and growth factor supplementation for management of hematological side effects in HIV/hepatitis C virus patients receiving pegylated-interferon and ribavirin.

BACKGROUND: Pegylated-interferon (PEG-IFN) and ribavirin (RBV), current standard treatment for hepatitis C virus (HCV) infection, are frequently associated with neutropenia and anemia, leading to high treatment discontinuation rates in HIV/HCV-coinfected patients. Our objective was to compare the effectiveness of intervening with hematologic growth factors versus dose reductions of standard HCV therapy for the management of treatment-induced hematologic disorders. METHODS: Ninety-two HIV/HCV-coinfected, therapy-naive subjects received PEG-IFN alfa-2b 1.5 µg·kg⁻¹·wk⁻¹ and RBV 13 ± 2 mg·kg⁻¹·d⁻¹ for up to 48 weeks. Before treatment initiation, subjects were randomized to subsequently receive growth factors, recombinant human erythropoietin (rHuEPO) and/or granulocyte colony-stimulating factor, or dose reduction (RBV and/or PEG-IFN) for anemia and neutropenia management, respectively. We analyzed the ability of each management strategy to control anemia and neutropenia and the percentage of subjects who achieved a successful treatment outcome according to the different management strategies. RESULTS: During treatment, 43 subjects developed anemia (human erythropoietin, n = 24; dose reduction, n = 19), whereas 25 subjects developed neutropenia (granulocyte colony-stimulating factor, n = 10; dose reduction, n = 15). After the intervention, the increase in both hemoglobin and absolute neutrophil counts did not differ between the 2 side effect management strategies. Sustained response percentages were similar comparing anemic and neutropenic subjects regardless of management strategy (anemia: recombinant human erythropoietin, 29% versus dose reduction, 21%, P = 0.92; neutropenia: granulocyte colony-stimulating factor, 40% versus dose reduction, 20%, P = 0.46). CONCLUSIONS: Growth factor supplementation and dose reduction do not seem to differ as management strategies for anemia and neutropenia in HIV/HCV-coinfected individuals treated with PEG-IFN/RBV.