|Hepatic toxicity (elevated AST, ALT, clinical hepatitis)
(NVP, TPV of particular concern)
NNRTI and PI therapy:
Within 12 weeks of initiation.
Within months to years of initiation.
Any ARV combination regimen:
Early due to IRIS.
Asymptomatic elevation of AST, ALT.
May be associated with symptoms of clinical hepatitis including nausea, fatigue, and jaundice.
AST, ALT elevations while on NVP, ABC, or RAL may be associated with skin rash or a hypersensitivity reaction.
HBV-coinfected patients may develop severe hepatic flare with initiation, withdrawal, or when resistance develops with 3TC, FTC, and TDF.
NRTIs, especially ZDV, ddI, and d4T, may be associated with lactic acidosis and hepatic steatosis.
|Uncommon in children.
Frequency varies with different agents and drug combinations.
HBV or HCV coinfection
Elevated baseline ALT, AST
Other hepatotoxic medications
Underlying liver disease
For NVP-associated hepatic events in adults:
Female with pre-NVP CD4 count >250 cells/mm3
Male with pre-NVP CD4 count >400 cells/mm3
Certain HLA types are also associated with NVP-associated hepatic events but are population-specific.a
Higher drug concentrations for PIs, particularly TPV
Avoid concomitant use of hepatotoxic medications.
If hepatic enzymes are elevated >5–10 times ULN, most clinicians would avoid NVP.
For ARVs other than NVP:
Obtain AST, ALT at baseline and thereafter at least every 3–4 months or more frequently in at-risk patients (such as HBV- or HCV-coinfected or elevated baseline AST, ALT).
Obtain AST, ALT at baseline, at 2 and 4 weeks, then every 3 months.
|If a symptomatic hepatic event occurs on NVP, permanently discontinue drug (see also NVP hypersensitivity).
In asymptomatic patients with ALT or AST >5–10 times ULN, some may consider discontinuing ARVs, others may continue therapy and monitor patient closely.
In symptomatic patients, discontinue all ARVs and other potential hepatotoxic agents and avoid restart of the offending agent.
When clinical hepatitis is associated with lactic acidosis, avoid restart of the most likely agent, and ZDV, d4T, and ddI in particular (see also lactic acidosis).
Rule out coinfection with HAV, HBV, HCV, EBV, and CMV.
Early in therapy
Asymptomatic elevation of indirect bilirubin levels with normal direct bilirubin, AST, and ALT.
|HIV-infected children receiving ATV: 49% developed increased total bilirubin levels (≥3.2 mg/dL); 13% had jaundice/scleral icterus.
||Not associated with HBV or HCV
No specific monitoring.
|Not necessary to discontinue the offending agent except for cosmetic reasons (hyperbilirubinemia may improve over time).
|Non-cirrhotic portal hypertension
||ARVs, especially ddI, d4T and combination of ddI and d4T
Late in therapy
GI bleeding, esophageal varices, hypersplenism.
Mild elevations in AST and ALT, moderate increases in ALP, and pancytopenia (because of hypersplenism).
Liver biopsy may reveal a variety of findings, most commonly nodular regenerative hyperplasia
or hepatoportal sclerosis
Probably less than 1%
|Prolonged exposure to ARV therapy, especially ddI and the combination of ddI and d4T
No specific monitoring.
|Manage complications of GI bleeding and esophageal varices.