title: Hyaluronic acid levels predict increased risk of non-AIDS death in hepatitis-coinfected persons interrupting antiretroviral therapy in the SMART Study.
abstract: BACKGROUND
  In the SMART study, HIV-viral-hepatitis-coinfected persons were, compared with HIV-monoinfected persons, at higher risk of non-AIDS death if randomized to the antiretroviral therapy (ART) interruption strategy. We hypothesized that a marker of liver fibrosis, hyaluronic acid (HA), would be predictive of development of non-AIDS-related outcomes in coinfected participants in the SMART study.
  
  
  METHODS
  All participants positive for HCV RNA or hepatitis B surface antigen (HBsAg) and with stored plasma samples were included (n=675). Plasma samples were tested for HA (normal range 0-75 ng/ml) at baseline and months 6, 12 and 24 during follow-up in the drug conservation (DC; interrupt ART until CD4(+) T-cell count <250) group and the viral suppression (VS; continued use of ART) group. Time to non-AIDS death was investigated using Kaplan-Meier analysis.
  
  
  RESULTS
  Overall, 52 (31 in DC and 21 in VS) coinfected participants died during follow-up. Coinfected participants who were randomized to the DC group with baseline HA>75 ng/ml had a cumulative risk of non-AIDS death of 24.6% after 36 months of follow-up compared with 9.3% for participants randomized to the VS group (P=0.005), while the cumulative risk for coinfected participants with HA ≤ 75 ng/ml was 4.1% (DC) and 4.7% (VS; P=0.76). The change in HA from baseline to month 24 was 8.3 ng/ml and 4.7 ng/ml in the DC and VS group (P=0.56), respectively.
  
  
  CONCLUSIONS
  Interruption of ART was particularly unsafe in HIV-hepatitis-coinfected individuals if plasma HA was increased. HA changed very little during follow-up and was not influenced by differences in CD4(+) T-cell count or HIV viral load.
authors.forename: Lars
authors.initials: L
authors.lastname: Peters
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Neuhaus
authors.forename: Amanda
authors.initials: A
authors.lastname: Mocroft
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
authors.forename: Jürgen
authors.initials: J
authors.lastname: Rockstroh
authors.forename: Gregory
authors.initials: G
authors.lastname: Dore
authors.forename: Massimo
authors.initials: M
authors.lastname: Puoti
authors.forename: Ellen
authors.initials: E
authors.lastname: Tedaldi
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Bernd
authors.initials: B
authors.lastname: Kupfer
authors.forename: Jens D
authors.initials: JD
authors.lastname: Lundgren
authors.forename: Marina B
authors.initials: MB
authors.lastname: Klein
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000378:metabolism; D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D035061:Control Groups; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006678:HIV / Q000187:drug effects; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D006509:Hepatitis B / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D006514:Hepatitis B Surface Antigens / Q000276:immunology / Q000378:metabolism; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D006801:Humans; D006820:Hyaluronic Acid / Q000096:biosynthesis / Q000097:blood*; D053208:Kaplan-Meier Estimate; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D006514:Hepatitis B Surface Antigens; D006820:Hyaluronic Acid