Tuesday, August 11, 2015

Initiation AntiRetroViral in Liver Disease

  • All classes of ARV agents have been associated with liver toxicity, so extra caution is warranted in prescribing HAART for patients with chronic liver disease. 
  • NVP and RTV have been associated with the highest risk of liver toxicity and should therefore be avoided if other options exist
  • For patients with chronic hepatitis B (HBV) infection, inclusion of 3TC and/or TDF in the HAART regimen should be considered because these agents are potent inhibitors of HBV replication 
  • However, patients who have a history of 3TC monotherapy while co-infected with HBV and HIV likely developed HIV resistance to 3TC, compromising the efficacy of this agent in HAART regimens. 
  • Discontinuation of either of these agents in a patient with chronic HBV can be associated with an acute exacerbation of HBV
  • Patients with chronic viral hepatitis (eg, hepatitis B virus [HBV], hepatitis C virus [HCV]) are at increased risk for drug-associated hepatotoxicity


Coinfection with Hepatitis B
  •  We do not treat patients for chronic HBV until they are ready to be treated for HIV
  • depends upon the patient’s prior treatment history for HIV and/or HBV, as well as their renal function
  • Treatment-naïve and normal or near-normal kidney function
    • tenofovir-emtricitabine (coformulated as Truvada) provides optimal coverage for the treatment of HIV when combined with a third agent (ie, protease inhibitor, integrase inhibitor, non-nucleoside reverse transcriptase inhibitor)
  • Treatment-experienced and normal or near-normal kidney function 
    • Tenofovir also suppresses HBV DNA in patients who are treatment-experienced (eg, previously received lamivudine, emtricitabine and/or entecavir) 
    • Such patients are most often those who received certain nucleoside backbones for their HIV, such as abacavir-lamivudine or zidovudine-lamivudine.
  • Treatment-naïve with reduced kidney function 
    • Entecavir can be used as a single agent for the treatment of HBV in patients with a baseline estimated creatinine clearance <50 mL/min/1.73m2 since HBV resistance to this agent rarely develops in patients who are treatment-naïve. 
    • The dose of entecavir must be adjusted according to renal function 
    • However, patients treated with entecavir must also be treated with a separate, fully suppressive HIV regimen

Coinfection with Hepatitis C
  • ART-naïve HIV/HCV-coinfected patients should be initiated on ART for their HIV disease, regardless of their CD4 cell count
  •  In most instances, it is preferable to start ART first and begin HCV therapy later. 
  • However, it is reasonable to delay ART initiation until after HCV treatment among patients with a CD4 cell count above 500 cells/microL
  • HCV treatment
    • Because the efficacy of direct-acting antiviral-containing regimens among HIV/HCV coinfected patients overall appears to be comparable to that among HCV monoinfected patients, decisions on regimen selection are similar between the two groups
    • Recommended to use direct-acting antivirals such as sofosbuvir, ledipasvir, ombitasvir-paritaprevir-ritonavir, dasabuvir, and simeprevir  
    • Other less preferable regimens may be warranted for patients who cannot defer therapy but live in locations where these agents are unavailable
Monitoring
  • Increased transaminase levels are usually asymptomatic and most elevations revert to normal levels despite continuation of the implicated drugs. 
  • However, some authorities recommend careful monitoring when aminotransferases reach five times the upper limit of normal (grade 3 toxicity)
  • ART should also be stopped in the event of symptomatic hepatotoxicity (eg, right upper quadrant pain, nausea, vomiting, jaundice). 
  • Clinicians should be aware that the risk of drug-induced liver injury is higher in patients with underlying chronic viral hepatitis
References:
  1. http://www.chartcaribbean.org/
  2. www.uptodate.com
  3. https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/10/initiating-art-in-treatment-naive-patients
  4. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents

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