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HIV Rebound Linked to Liver Fibrosis Progression in HIV/HCV Coinfected

HIV-positive people with hepatitis C virus (HCV) experienced progression to liver fibrosis if their HIV viral load rebounded above 1000 copies/mL or remained detectable on 2 consecutive tests, researchers reported in the January edition of HIV Medicine. Smaller transient HIV "blips," however, were not associated with worsening fibrosis. Optimized antiretroviral therapy, the study authors suggested, may protect the liver.

HIV/HCV coinfected people are known to experience more rapid liver fibrosis progression than people with hepatitis C alone, though the reason for this is not fully understood. SMART and other studies have shown that interruption of antiretroviral therapy (ART) and lack of HIV viral suppression are associated with liver, heart, and kidney disease, but it is not known what level of viremia affects liver fibrosis progression.

Curtis Cooper and fellow investigators with the Canadian Co-infection Cohort Study looked at the relationship between HIV viral load and fibrosis progression in 288 HIV/HCV coinfected people in the cohort. A majority (74%) were men, the mean age was 45 years, and the median CD4 T-cell count was 440 cells/mm³. Most (81%) reported a history of injection drug use and half currently drank alcohol.

Participants were on combination ART at baseline and had undetectable HIV RNA (<50 copies/mL) on 2 consecutive visits. At study entry they did not have fibrosis -- as estimated by the AST-to-Platelet Ratio Index or APRI, a non-invasive biomarker index (APRI <1.5) -- or end-stage liver disease, and they were not being treated for hepatitis C.

HIV rebound was defined as either HIV RNA >50 copies/mL on 2 consecutive visits or a single HIV RNA measurement >1000 copies/mL. An HIV blip was defined as a single viral load between 50 and 1000 copies/mL, preceded and followed by undetectable values. 

Results

• 57 participants (20%) progressed to an APRI score >1.5, indicating fibrosis, over a mean follow-up period of 1.1 years, for an incidence rate of 12.4 per 100 person-years.
• HIV viral rebound was a significant predictor of progression to APRI >1.5 (hazard ratio [HR] 2.3, or more than double the risk).
• HIV blips, however, were not associated with progression to fibrosis (HR 0.5).
• Each additional 1 log copies/mL of cumulative exposure to HIV viremia was associated with a 20% increase in the risk of fibrosis progression (HR 1.2).

"Liver fibrosis progression was associated with HIV rebound, but not blips, and with increasing cumulative exposure to HIV RNA, highlighting the importance of achieving and maintaining HIV suppression in the setting of HIV/HCV coinfection," the study authors concluded

"There are several proposed mechanisms by which non-suppressed HIV viremia may contribute to accelerated fibrosis," they noted in their discussion. "These include impaired HCV-specific immune response and cytokine deregulation leading to increased inflammatory milieu within the liver leading to activation of profibrotic processes and the potential for greater drug-induced hepatotoxicity. Increased microbial translocation from the gut during periods of viral rebound may contribute to increased concentrations of inflammatory markers (i.e. tumour necrosis factor alpha and interleukin-6) within the liver parenchyma contributing to increased fibrosis progression."

"Optimizing antiretroviral adherence, which would reduce the frequency of virological rebound episodes, may protect the liver from HCV-induced liver fibrosis progression," they recommended.

2/5/15

Reference

C Cooper, K Rollet-Kurhajec, J Young, et al (Canadian Co-infection Cohort Study Investigators). HIV virological rebounds but not blips predict liver fibrosis progression in antiretroviral-treated HIV/hepatitis C virus-coinfected patients. HIV Medicine 16(1):24-31. January 2015.