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Low CD4s, High Viral Load Tied to Progression to Advanced Liver Fibrosis
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Conference on Retroviruses and Opportunistic Infections (CROI), February 22-25, 2016, Boston
Mark Mascolini
Both low CD4 counts and high viral loads predicted progression to advanced liver fibrosis in a 3-year US analysis of 14,000 people with HIV with or without HCV [1].
HCV coinfection accelerates progression to fibrosis in people with HIV, noted CNICS Cohort researchers who conducted this study. But less is known about how HIV disease severity by itself affects progression risk in people with and without HCV. To address that question, they conducted this study of HIV-monoinfected and HIV/HCV-coinfected people in CNICS, a prospective observational cohort of HIV-positive people across the United States.
The study included everyone who entered CNICS on or after January 1, 2000, had at least two FIB-4 scores and 6 months of follow-up, and had an initial FIB-4 score below 1.45, indicating no significant fibrosis. Follow-up continued to March 2014. FIB-4 at or above 3.25 predicts advanced fibrosis, liver-related clinical outcomes, and overall mortality.
The analysis focused on 14,198 people with a median age of 38. Most cohort members (82%) were men, 46% were white, 34% black, and 14% Hispanic. HIV transmission risk factors were sex between men in 58%, heterosexual sex in 26%, and injecting drugs in 11%. There were 12,532 people (88%) infected with HIV but not HCV, 1666 people (12%) with chronic HCV infection, 1319 (9%) with alcohol use disorder, and 530 (4%) with diabetes. While 62% had a CD4 count above 349, 61% had a viral load below 500. Median initial FIB-4 stood at 0.8 (interquartile range 0.6 to 1.0).
During a median 3 years of follow-up, 1386 people (10%) had progression to advanced fibrosis (FIB-4 at or above 3.25) for an incidence of 2.2 per 100 person-years (meaning 2 of every 100 people had progression every year).
People with more advanced, poorly controlled HIV infection, as indicated by lower CD4 counts or higher viral loads calculated over time, ran a higher risk of progression to advanced fibrosis in Cox proportional hazards models. Compared with people who had more than 500 CD4 cells/mm(3), those with 350 to 500 had a 30% higher risk of progression (adjusted hazard ratio [aHR] 1.3, 95% confidence interval [CI] 1.1 to 1.5, P = 0.002), those with 200 to 349 CD4s had a doubled risk (aHR 1.9, 95% CI 1.6 to 2.2, P < 0.001), those with 100 to 199 CD4s had a tripled risk (aHR 2.9, 95% CI 2.4 to 3.5, P < 0.001), and those with fewer than 100 CD4s had a 7 times higher risk (aHR 6.9, 95% CI 5.8 to 8.3, P < 0.001). Each of those sub-500 CD4 brackets independently predicted development of advanced fibrosis in the 12,532 people with HIV infection alone. And all but a count of 350 to 500 independently predicted advanced fibrosis in the 1666 people coinfected with HCV.
The same pattern held true for each higher viral load bracket when compared with a sub-500 load: 500 to 9999 copies, 10,000 to 99,999 copies, and 100,000 or more copies. People with both a CD4 count below 200 and a viral load above 500 had more than a 7 times higher risk of advanced fibrosis (aHR 7.3, 95% CI 6.4 to 8.3).
Five other variables predicted progression to advanced fibrosis in the overall analysis and often in the analyses of HIV-monoinfected people and HCV-coinfected people, at the following adjusted hazard ratios (aHR) and 95% confidence intervals (in the overall analysis):
-- Chronic HCV: aHR 1.9, 95% CI 1.6 to 2.1, P < 0.001
-- Chronic HBV: aHR 1.5, 95% CI 1.2 to 1.8, P = 0.001
-- Alcohol use disorder: aHR 1.4, 95% CI 1.2 to 1.6, P < 0.001
-- Diabetes mellitus: aHR 1.9, 95% CI 1.6 to 2.3, P < 0.001
-- Every unit higher initial FIB-4: aHR 3.9, 95% CI 3.2 to 4.7, P < 0.001
Neither race nor gender predicted advanced fibrosis in this analysis.
The CNICS researchers believe their findings "underscore the potential role of virus-mediated liver injury independent of immune depletion and suggest that early and effective treatment of HIV infection could mitigate liver disease progression."
Reference
1. Kim N, Nance R, Van Rompaey S, et al. Poorly controlled HIV infection is a risk factor for liver fibrosis in CNICS cohort. Conference on Retroviruses and Opportunistic Infections (CROI), February 22-25, 2016, Boston. Abstract 558.
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