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Study Finds Undetectable HIV Viral Load Slows Liver Disease Progression in HCV/HIV Coinfection
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"CONTROL OF HIV VIRAL LOAD THROUGH HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART) SLOWS DOWN LIVER FIBROSIS PROGRESSION IN HIV/HCV-COINFECTION AND MAKES IT THE SAME AS IN HCV-MONOINFECTION. THE PUERTO RICO-NEW YORK HEPATITIS C STUDY GROUP"
Reported by Jules Levin
Brief summary: Reported at EASL Conference. HCV/HIV coinfected patients with suppressed HIV RNA (<400 copies/ml) have similar Fibrosis Progression Rare as HIV-negative patients with hepatitis C. Coinfected patients with uncontrolled HIV viremia have more rapid FPR than patients with suppressed HIV RNA and than HIV-negative patients. This applies when CD4 count is <500. In coinfection, FPR is independently predicted by log HIV viral load, Ishak necroinflammatory score, age at HCV infection, and not by CD4 cell count and alcohol use. The study author said: when deciding when to begin HAART, "our data suggests a role for HAART to slow down HCV-related fibrosis progression, HAART should be considered when CD4 cells are <500".
Numerous studies show HIV accelerates HCV at least 2 times more quickly than HCV disease in monoinfected individuals, and some of these studies were conducted in the HAART. Norbert Brau from the Veterans Affairs Medical Center, Bronx NY, USA and Maribel Rodriguez (Fundacion de Investigacions de Diego, San Juan, PR) reported in the final day's oral session at EASL (April 14-18, 2004, Berlin) on what I think is the first study to examine the association between HIV viral in patients and HCV disease progression.
Upon reviewing patients at his center he found many HCV/HIV coinfected patients had mild fibrosis. This study was a retrospective chart review from 2000 to 2002 in the Bronx and PR. Patient inclusion criteria: chronic HCV, treatment naïve, liver biopsy with Ishak scoring, HIV+ & known HIV viral load 7 CD4 count. 656 patients with known date of HCV infection were included (278 HCV/HIV, 388 HCV). They calculated the Fibrosis Progression Rate (FPR)= Ishak fibrosis score (0-6)/duration of HCV infection; time to cirrhosis= 5/FPR (Ishak fibrosis scores 5-6=cirrhosis); Ishak Necroinflammatory Score (0-18); Ishak Fibrosis score (0-6).
PATIENT CHARACTERISTICS
(388 HCV+, 278 HCV/HIV)
Age: 45 yrs, 48 yrs, <0.001
Female sex: 21%, 19.8%
HCV genotype: G1 80%, 77%; G2 18%, 18%
HCV RNA (median): 880,000, 880,000 copies/ml
ALT, mean: 82, 88
Age at HCV infection, mean: 23, 22
Duration of HCV infection, mean: 25.2 yrs, 23 yrs, <0.001
Mode of infection:
-IDU: 56%, 71%, <0.001
-blood transfusion: 20%, 2%, <0.001
-high-risk sex: 14%, 23%, <0.001
daily alcohol in last 5 yrs, mean (g): 39, 32
-0 g/d: 51%, 60%, 0.025
-50+ g/d: 26%, 17%, 0.004
HIV RNA <400 copies/ml: 51%
CD4 cells, median, range: 376 (1-1550)
CD4 cells <200: 18%
%on HAART: >95% of coinfected patients on HAART
FIBROSIS PROGRESSION RATE by HIV VIRAL LOAD
HIV- and HIV+ had similar progression rate: 0.128 (HIV-) vs 0.136 (HIV+), p=0.29. Brau commented that a different patient group where less patients had undetectable HIV viral load might show a faster FPR than HIV-negative individuals.
HIV+ with HIV RNA <400 c/ml has similar FPR as HIV- (0.122).
Patients with uncontrolled viremia have significantly faster FPR: when HIV RNA is >100,000 c/ml, FPR is 0.196 (p=0.044), which is significantly faster (about 60% faster) than FPR for HIV RNA <400 (0.122) (p=0.005), and FPR is also faster than for patients with 400 to 99,000 HIV RNA (0.145, p=0.044).
Patients with HIV RNA >400 c/ml have faster FPR (0.151) than patients with HIV RNA <400 (0.122, p=0.013) and HIV- (0.128, p=0.015).
Patients with HIV RNA 400 to 99,000 have FPR of 0.145 compared to HIV RNA <400 (0.122) and this is not significant (p=0.053).
CD4 COUNT
Patients with >350 CD4s have slower FPR than <350 CD4s (0.121 vs 0.155) (p=0.005).
When CD4 count is <500: FPR is slower if HIV RNA <400 (0.123) than HIV RNA >400 (0.162) (p=0.005).
When CD4 count is 500 or more FPR is the same regardless of HIV RNA <400> (0.121FPR when HIV RNA is<400 and 0.118 when CD4 >400).
ESTIMATED TIME TO CIRRHOSIS BY KAPLAMN MEIER CURVE
Using Kaplan Meier Curve, median time to cirrhosis is about 10 years shorter in patients with >400 copies/ml (p=0.008) (55 vs 45 yrs).
FACTORS THAT MIGHT BE ASSOCIATED WITH FPR
UNIVARIATE LINEAR PROGRESSION ANALYSIS
ALL PATIENTS
Associated with FPR:
Ishak necroinflammatory score (<0.001)
Age at HCV infection (<0.001)
ALT level (100 IU/L) (<0.001)
Alcohol use in last 5 yrs (0.005)
Not Associated with FPR:
HCV risk factor parenteral
HIV+
Log HCV RNA
Male sex
HIV/HCV COINFECTION
Associated with FPR:
Log copies/ml HIV RNA (0.001)
CD4 cell count (0.023)
Not Associated with FPR:
Treatment with HAART
For all patients:
Ishak necroinflammatory score (<0.001), age at HCV infection (<0.001), and alcohol use in past 5 yrs (0.002) are independently & significantly correlated with FPR.
For Coinfected patients, significantly & independently Associated with FPR:
Log HIV RNA level (0.018)
Ishak necroinflammatory score (<0.001)
Age at HCV infection (<0.001)
Not associated:
CD4 count
Alcohol in past 5 yrs. Alcohol was no longer significant in this multivariate model.
NECROINFLAMMATORY GRADE (0-18)
What occurs regarding Necroinflammatory Score is similar to what is seen with Fibrosis Progression Rate. From this study and what we've seen from other studies FPR & Necroinflamatory activity are tied into each other.
HIV+ with HIV RNA >400 have significantly faster FPR (7.44) than HIV+ with HIV RNA <400 (6.52, p=0.028) and HIV- (6.50, p=0.007).
HIV- (6.50) and HIV+ with HIV RNA <400 (6.52) have same FPR.
CD4 count: Patients with CD4 count <350 have significantly faster FPR (7.72) than CD4 count>350 (6.35, p=0.001).
HIV+ (6.96) vs HIV- (6.50): no difference in Necroinflamatory Grade.
FIBROSIS STAGE (Ishak Score 0-6)
A little different. The differences in Fibrosis Stage are of less magnitude. HIV+ >400 have slightly worse stage (3.09) than HIV- (2.86, p=0.16) and HIV + <400 (2.65, p=0.042). CD4 count <350 has worse stage (3.32) than CD4 >350 (2.50) (p<0.001). HIV + and HIV- negative have about same stage of fibrosis.
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