Managing Acute Antiretroviral Complications

Posted by e-Medical PPT Thursday, October 4, 2012
Abacavir Hypersensitivity
Incidence: 3-5%
Symptoms:
Onset 4-6 wks after initiation of abacavir therapy
Fever, skin rash, fatigue, GI symptoms (nausea, vomiting, diarrhea, abdominal pain), and respiratory tract symptoms (pharyngitis, dyspnea, or cough)
Management:
Discontinue abacavir
Do not re-start abacavir; severe symptoms will recur within hours, including life-threatening hypotension and death

Acute Hepatotoxicity
Nearly all currently available ARV drugs have been associated with hepatotoxic reactions
NRTIs --> non-alcoholic fatty liver disease (NAFLD) and hepatic steatosis; longer term exposure (> 6 months)
NNRTIs --> first 3-12 weeks after starting therapy; often associated with other systemic symptoms of hypersensitivity
PIs --> first 3-12 weeks after starting therapy, mild to moderate in severity; increased risk in those with underlying HBV, HCV
Unconjugated hyperbilirubinemia with indinavir, atazanavir – not a toxic reaction

Antiretroviral Therapy and Hepatotoxicity
Liver enzyme elevations are common in patients initiating ART
Any elevation 30-50%
Severe elevations 10-15%
Some ARVs may predispose to liver enzyme elevations
Ritonavir, Nevirapine
Chronic viral hepatitis increases the risk of liver enzyme elevations (range 2.5-8 fold)
Reports of rapid HCV disease progression or acute “flares” of chronic hepatitis B or C after initiation of ART

Hepatic Steatosis
Mild to moderate liver enlargement due to fat accumulation
Diagnosed by U/S, CT, or MRI
Multifactorial:
Macrovesicular: alcohol, diabetes, obesity, protein-calorie malnutrition, total parenteral nutrition
Drugs: Vitamin A, steroids, synthetic estrogens or androgenic steroids
Microvesicular: Reye’s syndrome, acute fatty liver of pregnancy, drugs
Treatment: Remove cause, avoid alcohol

Stavudine and Didanosine During Pregnancy
Dear Health Care Provider letter (1/5/01):
3 deaths in pregnant women receiving d4T and ddI; each received both drugs throughout pregnancy (other drugs were atazanavir, nelfinavir, and nevirapine in one each)
2 infant deaths – one in utero, and the second after emergency C-section
Boxed warning:
“…The combination of ddI and d4T should be used with caution during pregnancy and is recommended only in the potential benefit outweighs potential risk.”

Acute Nevirapine Hepatotoxicity
Nevirapine hepatotoxicity
Incidence 8-18% in clinical trials; 2.5-11% symptomatic hepatitis – generally occurs in first 4-18 weeks of treatment
Fulminant hepatic failure < 1%
Reported in HIV-seronegative HCWs receiving NVP for post-exposure prophylaxis and pregnant women receiving ddI, d4T (MMWR; 2001)
Factors associated with increased risk:
Chronic hepatitis due to HBV, HCV
Women with CD4+ T cell counts > 250 cells/L (11.9% vs 0.9%)
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