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©2013 UpToDate ® Print Email Antiretroviral agents, class adversereactions - I Reaction Lactic acidosis Hepatotoxicity Hyperglycemia Defintion Gr III = AST/ALT 5-10 X ULN Gr IV = AST/ALT >10 X ULN FBG >126 mg/dL Frequency 1.3 percent NRTI recipients receiving AZT, d4T, or ddI; median onset at 4 mos NRTIs: d4T, ddl, ZDV (7 to 16 percent); PIs - (15 to 30 percent) especially RTV (dose related) ABC+NVP - hypersensitivity with hepatic necrosis, eosinophilia and rash; NNRTI: NVP-hepatotoxicity (15 percent); EFV (8 percent) 3 to 17 percent with PIs Agents NRTIs d4T+dDl >d4T> ddl >ZDV >3TC = ABC, FTC >TDF All antiretrovirals PIs Risk factors Prolonged use NRTI (especially d4T) Female, pregnancy, obesity, ribavirin, metformin HCV or HBV infection, ETOH, female sex Preexisting glucose intolerance Symptoms GI (abd pain, anorexia, nausea, vomiting), wasting, dyspnea, cardiac arrhythmias Asymptomatic or sx of hepatitis. Note: ↑ indirect bilirubin with IDV or ATV is inconsequential Polyuria, polydipsia, polyphagia, weight loss Lab Lactate >2 mmol/mL; life-threatening if >10 mmol/mL LFTs; liver biopsy is usually not helpful Fasting glucose >126 mg/dL Treatment Lactate 2-5 mmol/mL + Sx - D/C NRTI if sx severe Lactate level is 5-10 mmol/mL - D/C NRTIsLactate >10 mmol/mL (medical emergency) - D/C NRTIs + supportive care: ventilator, dialysis, IV HCO3 Hypersensitivity reactions to ABC or NVP (fever, eosinophilia, rash, systemic response usually in first 6 wks): D/C drug immediately and do not rechallenge Asymptomatic elevations of LFT (<10 X ULN): repeat LFTs every 1 to 2 wks Symptomatic or elevations of LFT (>10 X ULN) or hyperlactatemia or hypersensitivity (ABC or NVP): change regimen Use standard diabetes treatment with diet and exercise. Preferred hypo- glycemics are: metformin or thiazolidinediones. D/C PI only if uncontrolled hyperglycemia. Monitor None LFTs at baseline and at 4-6 wks FBS baseline, at 3-6 mo, then yearly Reproduced with permission from: Bartlett, JG. Pocket Guide; Adult HIV/AIDS Treatment, November 2003.

©2013 UpToDate ® Print Email Antiretroviral agents, class adversereactions - I Reaction Lactic acidosis Hepatotoxicity Hyperglycemia Defintion Gr III = AST/ALT 5-10 X ULN Gr IV = AST/ALT >10 X ULN FBG >126 mg/dL Frequency 1.3 percent NRTI recipients receiving AZT, d4T, or ddI; median onset at 4 mos NRTIs: d4T, ddl, ZDV (7 to 16 percent); PIs - (15 to 30 percent) especially RTV (dose related) ABC+NVP - hypersensitivity with hepatic necrosis, eosinophilia and rash; NNRTI: NVP-hepatotoxicity (15 percent); EFV (8 percent) 3 to 17 percent with PIs Agents NRTIs d4T+dDl >d4T> ddl >ZDV >3TC = ABC, FTC >TDF All antiretrovirals PIs Risk factors Prolonged use NRTI (especially d4T) Female, pregnancy, obesity, ribavirin, metformin HCV or HBV infection, ETOH, female sex Preexisting glucose intolerance Symptoms GI (abd pain, anorexia, nausea, vomiting), wasting, dyspnea, cardiac arrhythmias Asymptomatic or sx of hepatitis. Note: ↑ indirect bilirubin with IDV or ATV is inconsequential Polyuria, polydipsia, polyphagia, weight loss Lab Lactate >2 mmol/mL; life-threatening if >10 mmol/mL LFTs; liver biopsy is usually not helpful Fasting glucose >126 mg/dL Treatment Lactate 2-5 mmol/mL + Sx - D/C NRTI if sx severe Lactate level is 5-10 mmol/mL - D/C NRTIsLactate >10 mmol/mL (medical emergency) - D/C NRTIs + supportive care: ventilator, dialysis, IV HCO3 Hypersensitivity reactions to ABC or NVP (fever, eosinophilia, rash, systemic response usually in first 6 wks): D/C drug immediately and do not rechallenge Asymptomatic elevations of LFT (<10 X ULN): repeat LFTs every 1 to 2 wks Symptomatic or elevations of LFT (>10 X ULN) or hyperlactatemia or hypersensitivity (ABC or NVP): change regimen Use standard diabetes treatment with diet and exercise. Preferred hypo- glycemics are: metformin or thiazolidinediones. D/C PI only if uncontrolled hyperglycemia. Monitor None LFTs at baseline and at 4-6 wks FBS baseline, at 3-6 mo, then yearly Reproduced with permission from: Bartlett, JG. Pocket Guide; Adult HIV/AIDS Treatment, November 2003. Antiretroviral agents, class adversereactions - II Reaction Fat redistribution Hyperlipidemia Rash Frequency 4 to 50 percent NNRTI: 8 to 16 percent Agents Fat accumulation: PIs Lipoatrophy: NRTIs d4T>ddI>AZT. Also occurs without antiretrovirals. PI NNRTI - NVP >EFV and DLV PIs - increased risk with sulfonamide allergy NRTI - ABC* Risk No clear risks defined Risk for DVC - HBP, diet, obesity, genes, prior MI/stroke, diabetes, age NNRTI - 1st 12 wks Female Sx

4 to 50 percent NNRTI: 8 to 16 percent Agents Fat accumulation: PIs Lipoatrophy: NRTIs d4T>ddI>AZT. Also occurs without antiretrovirals. PI NNRTI - NVP >EFV and DLV PIs - increased risk with sulfonamide allergy NRTI - ABC* Risk No clear risks defined Risk for DVC - HBP, diet, obesity, genes, prior MI/stroke, diabetes, age NNRTI - 1st 12 wks Female Sx Fat accumulation - abd (visceral), buffalo hump, breasts, lipomas Fat atrophy - extremities buttocks, face Cardiovascular disease with stroke or MI Common - red rash Severe - Stevens-Johnson synd, TEN, DRESS (Drug Rash, Eosinophilia, and Systemic Systems)* Lab CT scan, MRI, Waist: Hip, Bioelectric Impedence, DEXA, Ultrasound ↑ triglycerides ↑ cholesterol, and LDL cholesterol Eosinophilia - variable Treatment Plastic surgery (but expensive) Exercise? Change PI to NNRTI? Lipoatrophy- d/c d4T, ddI or AZT NECP guidelines: - General: diet and exercise - LDL cholesterol ↑: Pravastatin or atorvastatin - Triglycerides ↑: Gemfibrozil or fenofibrate Most rashes do not require drug discontinuation Withdraw NNRTI if severe; may tolerate other NNRTI (NVP → EFV) Monitor Appearance Fasting lipid profile at baseline, at 3 to 6 months post HAART initiation, then yearly. More frequently if high risk or treated. * DRESS: Life threatening complication that is seen with NVP and ABC - usually in the first 6 weeks of therapy. Reproduced with permission from: Bartlett, JG. Pocket Guide; Adult HIV/AIDS Treatment, November 2003.