Date of Award

January 2017

Document Type


Degree Name

Medical Doctor (MD)



First Advisor

Merceditas Villanueva


Background: Studies have documented more rapid progression of HCV-associated liver fibrosis in patients co-infected with HIV. However, the natural history of HCV infection in both mono-infected and HIV co-infected patients remains highly variable. The patterns and predictors of fibrosis progression in the HIV/HCV co-infected population are not fully characterized. Given the invasiveness of serial liver biopsies, Fibrosis-4 score (FIB-4), a composite of serum biomarkers that correlate well with fibrosis stage, is increasingly used. We used FIB-4 to study the natural history of liver fibrosis progression among co-infected patients and evaluated predictors of progression to cirrhosis over 5 years prior to treatment with direct acting agents (DAAs).

Methods: Study subjects were selected from HIV/HCV co-infected patients receiving care at Yale-New Haven Hospital from February 2014 through April 2016 without advanced fibrosis 5 years prior to study entry. Annual FIB-4 scores dating back 5 years were calculated from the most recent FIB-4 score or the last FIB-4 prior to DAA treatment initiation. Baseline demographics and clinical characteristics including HCV genotype, antiretroviral regimen, HIV viral loads and CD4 counts were collected. Patients were further categorized based on FIB-4 progression over the course of 5 years. Univariate and multivariable logistic regression models were used to examine factors associated with FIB-4 progression and a p-value of 0.05 was chosen as the threshold for statistical significance.

Results: There were 93 patients evaluated including 65 men and 28 women; mean age of 56.7 years; 32.3% were white, 53.8% were black. Injection drug use (IDU) was the major risk factor for HCV acquisition (63.4%) and the most common genotype was genotype 1 (81.2%). The median CD4+ count was 564 cells/mm3, and the majority (88.4%) had HIV viral loads <50 copies/mL. Over 5 years, 25 (26.9%) had FIB-4 progress to >3.25 and 68 (73.1%) had FIB-4 remain <3.25. Demographic variables (age, gender, race/ethnicity, BMI, substance use), clinical variables (HIV viral load, CD4 count, ART use, HIV duration, HCV duration and viral load) and co-morbid conditions such as diabetes and hyperlipidemia did not differ significantly between those whose FIB-4 stayed below 3.25 and those whose FIB-4 progressed to above 3.25 in univariate and multivariable logistic regression models.

Conclusion: In this study of 93 HIV/HCV co-infected patients without baseline advanced fibrosis, 26.9% progressed to advanced fibrosis over the course of 5 years. We did not identify any statistically significant factors that predicted those who were more likely to progress, although clinically relevant factors such as absence of HIV virologic control, low CD4 count, and lack of statin use showed a trend towards significance and should be assessed in future studies in a larger cohort. Our findings highlight the importance of prioritizing all patients with HCV/HIV co-infection for HCV treatment.


This thesis is restricted to Yale network users only. It will be made publicly available on 06/12/2019