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Medicine (Baltimore). 2016 Jul;95(29):e4091. doi: 10.1097/MD.0000000000004091.

Liver fibrosis progression and clinical outcomes are intertwined: role of CD4+ T-cell count and NRTI exposure from a large cohort of HIV/HCV-coinfected patients with detectable HCV-RNA: A MASTER cohort study.

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aUniversity Department of Infectious and Tropical Diseases, University of Brescia and Brescia Spedali Civili General Hospital, Brescia bClinic of Infectious Diseases, "San Gerardo de' Tintori" Hospital, Monza, Italy cDepartment of Epidemiology, College of Public Health and Health Professions & College of Medicine, University of Florida, Gainesville, FL dClinic of Infectious Diseases of "Papa Giovanni XXIII" Hospital, Bergamo eInstitute of Clinical Infectious Diseases of Catholic University of Sacred Heart, Rome fClinic of Infectious Diseases, University of Bari, Bari gClinic of Infectious Diseases of "Azienda Ospedaliera SM. Annunziata", Firenze hClinic of Infectious Diseases of "Azienda Ospedaliera S. Anna", Ferrara iClinic of Infectious Diseases of "Istituti Ospitalieri", Cremona jInfectious Diseases Unit, University "Magna Graecia", Catanzaro, Italy.



Patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) suffer from faster progression of liver fibrosis (LF) and have greater risk of worse clinical outcomes. We evaluated predictors and incidence of these events in a large multicentre cohort.


We selected all HIV-infected patients starting a first-line combination antiretroviral therapy (cART), with detectable HCV-RNA, without exposure to interferon/ribavirin, with ≥2 fibrosis-4 index (FIB-4) classifications before cART. Kaplan-Meier analysis was used to estimate incidence of clinical events (AIDS, non-AIDS related, deaths) and LF progression (via transitions: from FIB-4 class 1 to 2 or 3, from class 2 to class 3, and worsening by 0.5 point). Multivariate Cox regression was used to assess predictors, baseline, or time updated.


One thousand four hundred thirty-three patients were selected. Overall, 745 clinical events occurred, with an incidence of 7.6% over 9811 person-year of follow-up (PYFU) and a median survival time of 9.36 years. Incidence of LF progression from FIB-4 class 1 to 2 or 3 was 12.4%, and from FIB-4 class 2 to 3 was 7% with a median survival time of 5.67 and 10.35 years, respectively. At multivariate analyses, intravenous drug use and time-updated gamma-glutamyl transferase (γGT) were negative predictors for any outcomes, either clinical or FIB-4 progression. Higher CD4+ T-cell protected from clinical events, and lower HIV-RNA and higher CD4+ T-cell appeared to protect from FIB-4 transitions. Moreover, independently from the viro-immunological status, current FIB-4 class 3 predicted clinical events. Occurrence of AIDS and cardiovascular/kidney events were significant predictors of 0.5 point worsening and transitions of FIB-4, respectively. Prolonged exposure to nucleos(t)ide reverse transcriptase inhibitors (NRTI) was a negative predictor for any outcomes.


Both clinical and LF progression in HIV/HCV-coinfected patients depend strongly on immune status. Intravenous drug users and patients with high γGT (a possible proxy for alcohol abuse) are most-at-risk for both outcomes, as well those who had prolonged exposures to the NRTI class. Therefore, these patients should be prioritized for the access to anti-HCV therapy and a test-and-treat strategy should be implemented for early initiation of cART. Possible benefits of NRTI sparing regimens in HIV/HCV-coinfected patients should be investigated.

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