(Last updated: March 1, 2016; last reviewed: March 1, 2016)
|Adverse Effects||Associated ARVs||Onset/Clinical Manifestations||Estimated Frequency||Risk Factors||Prevention/ Monitoring||Management|
Elevated AST, ALT, clinical hepatitis
|All ARVs may be associated with hepatitis. NVP and TPV are of particular concern.
NVP, EFV, ABC, RAL, and MVC have been associated with hypersensitivity reactions.
NRTIs (especially ZDV, ddI, and d4T) are 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 and AST
Other hepatotoxic medications (including herbal preparations such as St. John's wort [Hypericum perforatum], Chaparral [Larrea tridentate], Germander [Teucrium chamaedrys])
Underlying liver disease
For NVP-Associated Hepatic Events in Adults:
For ARVs Other Than NVP:
|Asymptomatic patients with elevated ALT or AST should be evaluated for other causes and monitored closely (including repeating AST and ALT and checking total bilirubin). If ALT or AST is more than 5–10 times ULN and felt to be possibly or probably associated with ARVs, the potentially offending ARVs should be discontinued.
In symptomatic patients, discontinue all ARVs and other potential hepatotoxic agents and avoid restarting the offending agent.
If a symptomatic hepatic event occurs on NVP, permanently discontinue drug (see also NVP Hypersensitivity).
When clinical hepatitis is associated with lactic acidosis, avoid restarting the most likely agent, including ZDV, d4T, and ddI in particular (see also Lactic Acidosis).
Consider viral causes of hepatitis: HAV, HBV, HCV, EBV, and CMV.
|Indirect Hyper-bilirubinemia||IDV, ATV (with either RTV or COBI)||Onset:
||HIV-Infected Children Receiving ATV:
||Not necessary to discontinue the offending agent except for cosmetic reasons.
After an initial rise over the first few months of therapy, unconjugated bilirubin levels generally stabilize; in some patients, levels improve over time.
|Non-Cirrhotic Portal Hypertension||ddI, d4t||Onset:
||Prolonged exposure to ARV therapy, especially ddI and the combination of ddI and d4T||Monitoring:
||Manage complications of GI bleeding and esophageal varices.
Discontinue/ replace d4T or ddI, if patient is receiving either.
a For example, HLA-DRB1*0101 in whites, HLA-DRB1*0102 in South Africans, and HLA-B35 in Thai and whites.
Key to Acronyms: 3TC = lamivudine; ABC = abacavir; ALP = alkaline phosphatase; ALT = alanine transaminase; ARV = antiretroviral; AST = aspartate aminotransferase; ATV = atazanavir; CD4 = CD4 T lymphocyte; CMV = cytomegalovirus; COBI = cobicistat; d4T = stavudine; ddI = didanosine; EBV = Epstein-Barr virus; EFV = efavirenz; FTC = emtricitabine; GI = gastrointestinal; HAV = hepatitis A virus; HBV = hepatitis B virus; HCV = hepatitis C virus; HLA = human leukocyte antigen; IDV = indinavir; IRIS = immune reconstitution inflammatory syndrome; MVC = maraviroc; NRTI = nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; RAL = raltegravir; RTV = ritonavir; TDF = tenofovir disoproxil fumarate; TPV = tipranavir; ULN = upper limit of normal; ZDV = zidovudine