Increased incidence of antiretroviral drug discontinuation among patients with viremic hepatitis C virus coinfection and high hyaluronic acid, a marker of liver fibrosis.
BACKGROUND
Most antiretroviral drugs are metabolized by the liver; hepatic disease or liver damage as a result of hepatitis C virus (HCV) could impair this metabolism leading to an increased risk of drug toxicity. This study aimed to determine the risk of antiretroviral drug discontinuation among HCV/HIV coinfected patients.


METHODS
EuroSIDA patients taking combination antiretroviral therapy were included. Poisson regression identified factors associated with antiretroviral treatment discontinuation.


RESULTS
A total of 9535 HIV-positive patients with known HCV status were included (6939 HCVAb-negative; 2596 HCVAb-positive at baseline). Viremic HCV infection was associated with a 44% increased risk of antiretroviral drug discontinuation compared with aviremic infection [adjusted incidence rate ratio, aIRR: 1.44 (95% confidence interval, CI 1.22-1.69)]; this relationship was largest among nonnucleoside reverse transcriptase inhibitors [aIRR: 1.59 (95% CI 1.18-2.14)]. In the subset of 935 HIV-positive patients also HCV-positive or HBV-positive with plasma hyaluronic acid measured, hyaluronic acid more than 100 ng/ml was associated with a 37% increased risk of antiretroviral drug discontinuation [aIRR: 1.37 (95% CI 1.08-1.73) vs. hyaluronic acid ≤100 ng/ml] and the effect of HCV viremia became nonsignificant; the largest drug association was seen for protease inhibitors [aIRR: 1.40 (95% CI 1.04-1.89)].


CONCLUSIONS
HCV viremia and high levels of hyaluronic acid predict antiretroviral drug discontinuation. Evidence was also found to suggest a link between impaired liver function and protease inhibitor toxicity.
aDepartment of Infection and Population Health, University College London, London, UK bCopenhagen HIV Programme, University of Copenhagen cDepartment of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark dDepartment of Medicine I, University of Bonn, Bonn, Germany eDepartment of Infectious Diseases, Saint-Pierre Hospital, Brussels, Belgium fInfectious Diseases Department, Gomel State Medical University, Gomel, Belarus gDepartment of Infectious Diseases, Medical University, Wroclaw, Poland hInfectious Diseases Department, Odense University Hospital, Odense, Denmark.
Daniel
D
Grint
Lars
L
Peters
Juergen K
JK
Rockstroh
Stephane
S
de Wit
Victor M
VM
Mitsura
Brygida
B
Knysz
Court
C
Pedersen
Ole
O
Kirk
Jens D
JD
Lundgren
Amanda
A
Mocroft
D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D060085:Coinfection / Q000175:diagnosis; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D016174:Hepacivirus / Q000302:isolation & purification*; D006526:Hepatitis C / Q000150:complications / Q000175:diagnosis*; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood*; D008103:Liver Cirrhosis / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014766:Viremia / Q000175:diagnosis; D016903:Drug Monitoring
D044966:Anti-Retroviral Agents; D006820:Hyaluronic Acid