EACS 2011: Antiretroviral Therapy Reduces Liver Fibrosis Progression in HIV/HCV Coinfected People

Earlier initiation of antiretroviral therapy (ART) and spending more time on HIV treatment may help slow liver disease progression in HIV/HCV coinfected patients, according to an Italian study using non-invasive methods presented at the 13th European AIDS Conference (EACS 2011) last week in Belgrade.

HIV positive people with hepatitis C virus (HCV) coinfection typically experience more rapid liver fibrosis progression and respond less well to interferon-based therapy than individuals with HCV alone. Since the advent of effective combination ART, liver disease has become a leading cause of death for people with HIV.

Massimiliano Fabbiani and colleagues investigated the incidence of and factors associated with fibrosis progression among HIV/HCV coinfected participants in the Italian MASTER cohort who started combination ART between 1996 and 2010.

Liver fibrosis was evaluated using the non-invasive FIB-4 index, which is calculated based on a person's age, levels of alanine and aspartate aminotransferase (ALT and AST, respectively), and platelet count. Non-invasive measures are not as accurate as "gold standard" liver biopsy -- especially for distinguishing intermediate fibrosis stages -- but it is less expensive, less uncomfortable, and carries a smaller risk of complications.

The analysis included 1568 participants followed from the time they initiated ART. Most (73%) were men, the median age was 36 years, and nearly three-quarters had a history of injection drug use. One-third had HCV genotypes 1 or 4, 15% had genotypes 2 or 3, and half had an unknown genotype.

Participants had relatively advanced HIV disease, with a median CD4 T-cell count of 256 cells/mm³ and a median CD4 nadir (lowest-ever level) of  80 cells/mm³; half had a history of AIDS-defining events. People with severe fibrosis, cirrhosis, or liver cancer at baseline, heavy alcohol users, and patients with hepatitis B triple infection were excluded.

Results

• At baseline, 62% of participants had a FIB-4 score reflecting stage 1 or mild fibrosis (< 1.45) and 38% had stage 2 or moderate fibrosis (1.46-3.25).
• During a median follow-up period of 54 months, 1113 patients (71%) transitioned to a higher FIB-4 fibrosis stage and 556 people (36%) progressed to stage 3 or severe fibrosis (FIB-4 > 3.25).
• The incidence of progression to a higher fibrosis stage was 0.23 per person-year of follow-up, while progression to stage 3 was 0.06 per person-year.
• In a multivariate analysis, factors independently associated with progression to a higher fibrosis stage included:

o      Older age: hazard ratio (HR) 2.15, or about twice the risk;

o      Past AIDS-defining events: HR 1.71.

• Factors predicting lower risk of fibrosis progression included:

o      Longer time on combination ART: HR 0.96 per additional 1 month on therapy;

o      Longer time with undetectable HIV viral load (< 50 copies/mL): HR 0.96 per 1 additional month.

• Looking at progression to severe fibrosis, significant risk factors were:

o      Older age: HR 1.88;

o      Higher baseline FIB-4 score (stage 2 rather than stage 1): HR 2.31.

• Factors associated with lower risk of severe fibrosis were:

o      Longer time on ART: HR 0.97 per 1 additional month;

o      More time with HIV viral load < 50 copies/mL: HR 0.97 per 1 additional month.

Based on these findings, the researchers concluded that "better viro-immunological control" on ART may slow liver fibrosis progression in coinfected patients and suggested that earlier initiation HIV treatment may be beneficial for this population.

Fabbiani noted that HCV genotype 3 was associated with a greater risk of fibrosis progression than genotype 1 in a univariate analysis, but this was no longer significant in a multivariate analysis controlling for other factors.

Asked to speculate on the reason for ART's protective effect, he suggested that antiretroviral treatment may have a beneficial anti-inflammatory effect beyond its impact on HIV viral load and CD4 cell count.

Investigator affiliations: Catholic University of S Heart, Clinical Infectious Diseases, Rome, Italy; University of Brescia, Institute of Infectious and Tropical Diseases, Brescia, Italy; Ospedali Riuniti, Bergamo, Italy; S. Anna Hospital, Ferrara, Italy; Istituti Ospitalieri, Cremona, Italy; S. Maria Annunziata Hospital, Florence, Italy; Policlinico di Bari, Bari, Italy.

10/18/11

Reference

M Fabbiani, S Di Giambenedetto, M Colafigli, et al. Predictors of Worsening Liver Fibrosis Evaluated through FIB-4 in HIV-HCV Co-infected Patients Starting Combined Antiretroviral Therapy (cART). 13th European AIDS Conference (EACS 2011). Belgrade, October 12-15, 2011. Abstract PS7/2.