The Era of DAAs: Assessing the Clinical Impact and Emergence of Comorbidities in HIV/HCV-Coinfected versus HIV-Infected Individuals

Author:

Álvarez-Álvarez Beatriz1,Prieto-Pérez Laura1,Cuadra-Grande Alberto de la2,Casado Miguel Ángel2,Úbeda Alfonso Cabello1,Al-Hayani Aws W.1,Acosta Irene Carrillo1,Mahillo-Fernández Ignacio3,Hernández-Mora Miguel Górgolas1,Rallón Norma4,Benito Jose M.4

Affiliation:

1. Division of Infectious Diseases. Hospital Universitario Fundación Jiménez Díaz

2. Pharmacoeconomics and Outcomes Research Iberia (PORIB)

3. Biostatistics and Epidemiology Unit. Instituto de Investigación Sanitaria-Hospital Universitario Fundación Jiménez Díaz, Universidad Autónoma de Madrid (IIS-FJD, UAM)

4. HIV and Viral Hepatitis Research Laboratory, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Universidad Autónoma de Madrid (IIS-FJD, UAM)

Abstract

Abstract

Background Human immunodeficiency virus (HIV) infection causes sustained chronic immune activation which is associated with earlier and more frequent onset of comorbidities. Coinfections, such as those caused by hepatitis C virus (HCV), amplify this immune status. However, direct-acting antivirals (DAAs) transformed HIV/HCV management by eradicating HCV quickly and effectively, bypassing the systemic proinflammatory and immunomodulatory effects of interferon regimens. HCV infection significantly impacts the immunopathogenesis of HIV, and eradication of HCV with DAAs improves, but does not entirely normalize, the levels of markers of systemic inflammation, endothelial dysfunction or T-cell activation and exhaustion. This study aimed to determine whether HIV-infected individuals versus individuals with HIV/HCV coinfection, in the era of interferon-free therapies, exhibit an increased incidence of comorbidities and non-AIDS-related events. Methods A retrospective analysis was conducted at a Spanish tertiary hospital, involving 229 HIV/HCV-coinfected patients and 229 HIV-infected patients, all with effectively controlled HIV. Coinfected patients underwent HCV clearance using DAAs and had no history interferon treatment. The incidences of hypertension, diabetes mellitus, cardiovascular disease, kidney disease, liver disease, non-AIDS cancer and death were compared between the groups. Univariate logistic regression models and subsequent multivariate adjustment for all factors potentially impacting outcomes were used to assess the risk of clinical event onset. Propensity score (PS) analyses were also conducted to support the multivariate model results. Results Univariate logistic regression analyses revealed that, compared to HIV/HCV coinfected patients, HIV monoinfected patients presented a greater risk for hypertension (Odds Ratio [OR] = 1.93; 95% Confidence Interval [CI] = 1.03–3.74; p = 0.040), dyslipidemia (OR = 1.83; 95%CI = 1.13–3.01; p = 0.014) and kidney disease (OR = 3.14; 95%CI = 1.19–9.80; p = 0.019) onset. Monoinfection was also associated with a lower risk for developing liver disease (OR = 0.12; 95%CI = 0.01–0.67; p = 0.012) and death (OR = 0.29; 95%CI = 0.06–0.96; p = 0.043). Multivariate models and PS showed that previous exposure to HCV was not associated with the onset of any clinical events studied. Conclusions Successful HCV elimination using DAAs improved the outlook regarding comorbidities and survival across both patient cohorts. Early HCV detection and DAA therapy could enhance clinical results. These findings provide an optimistic perspective for those living with HIV/HCV coinfection and underscore the importance of continuing efforts toward early detection and DAA treatment initiation.

Publisher

Research Square Platform LLC

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