BACKGROUND:Hepatitis C virus (HCV) has significantly impacted people with human immunodeficiency virus (HIV). Harm reduction programs, changing transmission patterns, and direct-acting antivirals (DAAs) have profoundly altered HIV/HCV coinfection trends. This study evaluates HCV prevalence among people with HIV in Spain over 2 decades. METHODS:We conducted 9 cross-sectional studies (2002-2023) in 39-43 centers. Sampled individuals were randomly sampled from people with HIV actively followed up at these centers, with proportional allocation. Main outcomes included the prevalence of anti-HCV antibody and active HCV infection (HCV RNA--positive result). RESULTS:The reference population ranged from 31 800 to 47 006, with sample sizes of 1260-1867. HIV transmission patterns shifted from 2002 to 2023, with injection drug use decreasing from 55% to 21% and the proportion of men who have sex with men increasing from 17% to 46%. HCV seroprevalence fell from 60.8% to 27.4%, and active infection from 46.3% to 0.9%. In the DAA era (2015-2023), active HCV infection dropped by 100% in heterosexuals, 94% in people who inject drugs, and 71% in men who have sex with men. Treatment uptake increased from 23% in 2002 to 99% by 2023 with all-oral DAAs. The prevalence of cirrhosis among active HCV cases peaked at 23.1% in 2015 but fell to 0% by 2021. Among those achieving sustained virologic response, cirrhosis prevalence was 20.4% in 2023. CONCLUSIONS:HIV/HCV coinfection has drastically declined in Spain, with active HCV infection prevalence <1% since 2021. DAAs were pivotal in this achievement. However, cirrhosis remains a concern among those with sustained virologic response. Ongoing surveillance and prevention efforts are essential to sustain these gains and address residual risks.
BACKGROUND:Dual antiretroviral therapy (ART) with dolutegravir/lamivudine (DTG/3TC) is widely used in virologically suppressed individuals. However, data remain limited on potential differential effects of ART regimens on mid-term systemic inflammation and metabolic health. We evaluated whether switching from DTG/3TC to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) modifies systemic inflammation or metabolic parameters. METHODS:INSTINCT was a phase IV, multicenter, open-label, randomized trial enrolling adults with HIV-1 on stable DTG/3TC and sustained viral suppression. Participants were randomized (1:1) to continue DTG/3TC or switch to BIC/FTC/TAF and followed for 96 weeks. Plasma biomarkers (sCD14, IL-6, sCD163, hsCRP, D-dimer, and kynurenine/tryptophan ratio) were measured at baseline, week 48, and week 96. Secondary outcomes included CD4⁺ and CD4/CD8 ratio, virological suppression, weight, lipid profile, and renal function. Longitudinal changes were analyzed using linear mixed-effects models. RESULTS:A total of 141 participants were randomized. Over 96 weeks, no significant between-group differences were observed in inflammatory biomarkers. CD4⁺ T-cell counts and CD4/CD8 ratio remained stable and comparable across arms. Weight changes were modest and similar; the proportion with ≥5% weight gain did not differ. No relevant differences were found in lipids, glucose, or eGFR. Virological suppression was maintained in >95% of participants. Adverse events were mild and balanced between groups. CONCLUSIONS:In virologically suppressed individuals, maintaining DTG/3TC or switching to BIC/FTC/TAF demonstrated equivalent profiles with respect to systemic inflammation, metabolic outcomes, and immunologic markers over 96 weeks.
In a large multicenter real-world cohort, we aimed to evaluate outcomes of FLAG-Ida salvage therapy for relapsed/refractory (R/R) acute myeloid leukemia (AML) and validated the SALFLAGE prognostic score. We analyzed 1079 adults with R/R AML treated across 112 PETHEMA institutions over 26 years (1998-2024), including patients with primary refractory disease (36.9%) and first relapse episode (63.1%), with a median age of 52 years. Complete remission composite (CRc) was achieved 56.8%, including complete remission (CR) in 51.0%, CR with incomplete recovery in 4.0%, and morphological-free-state in 1.8%, enabling 35.2% of patients and 62% of responders to proceed to allogeneic transplantation without morphological disease. With median follow-up of 50.9 months, median overall survival (OS) was 10.2 months, with 5-year OS rate of 21.6%. Prior allogeneic transplantation (HR 0.54; p < 0.001) and relapse-free interval ≥ 1 year (HR 0.75; p = 0.024) independently predicted improved OS, whereas modified high-risk cytogenetics including t(8; 21) (HR 3.58; p < 0.001), FLT3-ITD mutation at primary diagnosis (HR 1.61; p < 0.001), and age ≥ 60 (HR 1.43; p < 0.001) conferred inferior OS. Validation of the SALFLAGE score demonstrated moderate discrimination (C-index 0.67), with 5-year survival of 38.4%, 27.2%, and 12.7% across risk categories (p < 0.001). Outcomes improved over periods (1998-2005 vs. 2006-2016 vs. 2017-2024): 30-day mortality was 6.9% vs. 9.3% vs. 5.0%, respectively (p = 0.030), and median OS was 7.8 versus 9.4 versus 11.1 months, respectively (p = 0.16). We confirm FLAG-Ida as a reference salvage regimen in fit R/R AML and validate the SALFLAGE score in this setting.
OBJECTIVE:Risk of acute/recent hepatitis C virus infection (ARHCV) and bacterial sexually transmitted infections (STIs) among MSM (MSM-HIV) is heterogeneous. We aimed to identify clinical phenotypes and assess their association with incident ARHCV and bacterial STIs. DESIGN:A prospective multicenter cohort study. METHODS:Between 2022 and 2024, MSM-HIV were recruited from 10 centers in Madrid and followed for 12 months with HCV and bacterial STI screening. App-based questionnaires captured behavioral and mental health data. Thirty-eight variables were analyzed using principal component analysis and hierarchical clustering to derive clinical phenotypes. RESULTS:A total of 529 participants were included (median age 41 years). Three phenotypes were identified: CP1 (n = 328, 62.0%), CP2 (n = 133, 25.1%), and CP3 (n = 68, 12.9%), representing different levels of sexual risk, substance use, and prior STI/HCV history. ARHCV incidence was 0.94, 0.72, and 11.76 per 100 person-years in CP1, CP2, and CP3, respectively, and was higher in CP3 than in CP1 (incidence rate ratio [IRR] 12.49, 95% confidence interval [CI] 3.00-73.08) and CP2 (16.25, 2.18-720.93). Bacterial STI incidence was 33.29, 60.83, and 61.76 per 100 person-years, respectively, and was higher in CP2 (IRR 1.83, 95% CI 1.36-2.46) and CP3 (IRR 1.86, 95% CI 1.27-2.68) than in CP1. CONCLUSION:Clinical phenotypes stratified ARHCV and bacterial STI incidence among MSM-HIV. ARHCV was concentrated in a small high-exposure subgroup, whereas bacterial STIs were more frequent in intermediate and high-exposure phenotypes. Phenotype-based approaches may help guide risk stratification and prevention in HIV care.
