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Home > Treatment > Charts & Tables > ARV Adverse Effects
Adverse Effects of Antiretroviral Drugs
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Introduction
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Tables
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transparent imageNucleoside Reverse Transcriptase Inhibitors
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transparent imageNonnucleoside Reverse Transcriptase Inhibitors
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transparent imageIntegrase Inhibitors
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transparent imageProtease Inhibitors
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transparent imageChemokine Coreceptor Antagonists
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transparent imageFusion Inhibitors
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transparent imagePharmacokinetic Enhancers
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Introduction
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The following tables summarize the most common and most serious adverse events associated with antiretroviral medications used to treat HIV infection. For drug-drug interactions, see the Database of Antiretroviral Drug Interactions.

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Tables
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Nucleoside Reverse Transcriptase Inhibitors
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  • NRTIs are associated with lactic acidosis, hepatic steatosis, and body fat redistribution (lipodystrophy).

Drug Adverse Events Comments
Abacavir
  • Hypersensitivity syndrome (fever, myalgia, malaise, nausea, vomiting, symptoms suggestive of upper respiratory tract infection, anorexia); symptoms progressively worsen with each subsequent dose; rash occurs in about half of cases. This is associated with HLA-B*5701.

  • Rash

  • Headache, nausea, vomiting, diarrhea

  • Hypersensitivity reaction usually occurs in the first 6 weeks of treatment.

  • Hypersensitivity reaction may be more severe with once-daily abacavir dosing.

  • Risk of hypersensitivity related to HLA-B*5701; must screen for this before prescribing abacavir; do not use in persons who have this allele.

  • Counsel patients on signs of hypersensitivity syndrome.

  • In case of hypersensitivity syndrome, abacavir must be discontinued permanently.

Didanosine
  • Pancreatitis

  • Peripheral neuropathy

  • Nausea, diarrhea

  • High risk of adverse effects; avoid if possible.

  • Concomitant alcohol use may increase risk of pancreatitis.

  • Lower frequency of diarrhea with enteric-coated capsules.

  • Increased risk of lactic acidosis and hepatic steatosis when combined with stavudine; this combination should be avoided, especially during pregnancy.

  • Increased risk of peripheral neuropathy when combined with stavudine.

  • Adjust dosage for renal insufficiency or failure.

Emtricitabine
  • Headache, nausea, insomnia

  • Hyperpigmentation of palms and soles (occurs most frequently in dark-skinned people)

  • Adverse effects occur infrequently.

  • Active against hepatitis B virus (not approved by the U.S. Food and Drug Administration [FDA] for treatment of hepatitis B). In patients with HIV and hepatitis B coinfection, hepatitis may flare upon discontinuation of emtricitabine.

  • Adjust dosage for renal insufficiency or failure.

Lamivudine
  • Headache, dry mouth

  • Adverse effects occur infrequently.

  • Active against hepatitis B virus. In patients with HIV and hepatitis B coinfection, hepatitis may flare upon discontinuation of lamivudine.

  • Adjust dosage for renal insufficiency or failure.

Stavudine
  • Peripheral neuropathy

  • Pancreatitis

  • Dyslipidemia

  • Diarrhea

  • High risk of adverse effects; avoid if possible.

  • Of the NRTIs, stavudine appears to convey the greatest risk of lipodystrophy and other mitochondrial toxicity.

  • Increased risk of lactic acidosis and hepatic steatosis when combined with didanosine; this combination should be avoided, especially during pregnancy.

  • Increased risk of peripheral neuropathy when combined with didanosine.

  • Consider dosage adjustment for peripheral neuropathy.

  • Adjust dosage for renal insufficiency or failure.

Tenofovir alafenamide (TAF)
  • Kidney disease

  • Active against hepatitis B. In patients with HIV and hepatitis B coinfection, hepatitis may flare upon discontinuation of tenofovir.

  • Risk of kidney and bone adverse effects appears to be lower than with tenofovir DF.

  • Adjust dosage for renal insufficiency or failure.

Tenofovir disoproxil fumarate (TDF)
  • Kidney disease: acute kidney injury, Fanconi syndrome, chronic kidney disease

  • Osteopenia, osteoporosis

  • Flatulence, nausea, diarrhea, abdominal discomfort

  • Asthenia

  • Active against hepatitis B but not FDA approved for treatment of hepatitis B. In patients with HIV and hepatitis B coinfection, hepatitis may flare upon discontinuation of tenofovir.

  • Gastrointestinal symptoms may be worse in lactose-intolerant patients; TDF is formulated with lactose.

  • Adjust dosage for renal insufficiency or failure.

Zidovudine
  • Anemia, neutropenia

  • Fatigue, malaise, headache

  • Nausea, vomiting

  • Myalgia, myopathy

  • Hyperpigmentation of skin and nails

  • Higher risk of adverse effects than with some other NRTIs.

  • Fatigue, nausea, headache, and myalgia usually resolve 2-4 weeks after initiation.

  • Adjust dosage for renal insufficiency or failure.

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Nonnucleoside Reverse Transcriptase Inhibitors
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  • NNRTIs are associated with rash, and may cause Stevens-Johnson syndrome and toxic epidermal necrolysis.

  • All NNRTIs may have significant interactions with other drugs; dosage adjustment of interacting agents may be required.

Drug Adverse Events Comments
Delavirdine
  • Fatigue

  • Elevations in liver function tests, hepatitis

  • Nausea, diarrhea

  • Seldom used; less potent than other NNRTIs.

Efavirenz
  • Abnormal dreams, drowsiness, dizziness, confusion

  • Mood changes, including suicidality

  • Elevations in liver function tests

  • Hyperlipidemia

  • Central nervous system symptoms are common; severity usually decreases within 2-4 weeks.

Etravirine
  • Elevations in liver function tests

  • Tablets may be dissolved in water.

  • Interactions with other drugs may differ from those of first-generation NNRTIs; screen carefully for drug interactions before prescribing.

  • Does not interact with methadone.

Nevirapine
  • Elevations in liver function tests, hepatitis, liver failure

  • Initial dose of 200 mg per day for first 14 days, then 200 mg twice daily (immediate-release formulation) or 400 mg once daily (extended-release formulation), decreases frequency of rash.

  • Most rash develops within first 6 weeks of therapy; rash is most common in women.

  • Hepatotoxicity may be life threatening. It is more common at higher CD4 cell counts, in women, and in patients with hepatitis B or C. Nevirapine should not be initiated for women with CD4 counts of >250 cells/µL or men with CD4 counts of >400 cells/µL, unless the benefit clearly outweighs the risk. Monitor liver tests closely for the first 16 weeks of treatment.

Rilpivirine
  • Insomnia

  • Depression

  • Elevations in liver function tests

  • Elevations in serum creatinine

  • May be less potent if baseline HIV RNA >100,000 copies/mL

  • Requires acidic gastric environment for adequate absorption:
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    • Must be taken with food.

    • Contraindicated with proton pump inhibitors.

    • Other antacid medications and H2 blockers require specific timing if used by persons taking rilpivirine.

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Integrase Inhibitors
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  • Integrase inhibitors may cause rash, and rarely may cause hypersensitivity syndrome.

  • Polyvalent cations (eg, aluminum, calcium, iron, and magnesium cations) may interfere with gastrointestinal absorption of integrase inhibitors.

Drug Adverse Events Comments
Bictegravir
  • Nausea, diarrhea

  • Headache

  • Increase in serum creatinine

  • Rash

  • Inhibits tubular secretion of creatinine but has no effect on actual glomerular filtration rate.

Dolutegravir
  • Headache, insomnia, mood disturbance

  • Increase in serum creatinine

  • Rash

  • Inhibits tubular secretion of creatinine but has no effect on actual glomerular filtration rate.

Elvitegravir
  • Insomnia, abnormal dreams

  • Rash

  • Must be coadministered with a pharmacokinetic enhancer (currently available only in coformulations with cobicistat).

Raltegravir
  • Nausea, diarrhea, flatulence

  • Elevations in amylase and liver function tests

  • Headache

  • Dizziness, abnormal dreams

  • Pruritus, rash

  • Fatigue, muscle pain

  • Usually well tolerated.

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Protease Inhibitors
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  • All PIs are associated with metabolic abnormalities including dyslipidemia, hyperglycemia, insulin resistance, and lipodystrophy. (Atazanavir is less likely to cause dyslipidemia.)

  • PIs may increase the risk of bleeding in people with hemophilia.

  • PIs have significant interactions with many other drugs; dosage adjustment of interacting agents may be required.

Drug Adverse Events Comments
Atazanavir
  • Diarrhea, nausea

  • Hyperbilirubinemia, jaundice

  • Elevations in liver function tests

  • Gallstones, kidney stones

  • PR interval prolongation

  • Proton pump inhibitors interfere with atazanavir absorption and are contraindicated for use by patients receiving atazanavir.

  • Other antacid medications and H2 blockers also interfere with absorption of atazanavir and should be used with caution by patients receiving atazanavir.

  • Indirect hyperbilirubinemia; does not require discontinuation of atazanavir.

  • May have less effect than other PIs on lipid levels.

Darunavir
  • Diarrhea, nausea

  • Rash

  • Elevations in liver function tests

  • Must be coadministered with pharmacokinetic enhancer (cobicistat or ritonavir).

  • May cause rash in patients sensitive to or intolerant of sulfonamides.

  • Increases pravastatin (and other statin) levels; no significant interaction with atorvastatin.

Fosamprenavir
  • Diarrhea, nausea, vomiting

  • Elevations in liver function tests

  • Rash

  • Hyperlipidemia

  • Prodrug of amprenavir.

  • May cause rash in patients sensitive to or intolerant of sulfonamides.

Indinavir
  • Kidney stones, flank pain

  • Hyperbilirubinemia

  • Elevations in liver function tests

  • Alopecia, dry skin, ingrown nails

  • Insomnia

  • Taste perversion

  • High risk of adverse effects; avoid if possible.

  • To reduce risk of kidney stones, patients should drink at least 1.5 liters of fluid daily.

  • When used as sole PI, should be taken on an empty stomach, 1 hour before or 2 hours after a meal, and should be taken every 8 hours (not 3 times per day).

Lopinavir/ ritonavir
  • Diarrhea, nausea, vomiting

  • Dyslipidemia

  • Elevations in liver function tests

  • Taste perversion

  • Available in tablets or oral solution.

  • Oral solution contains 42% alcohol--avoid combining oral solution with metronidazole or disulfiram. Alcohol in the oral solution may cause disulfiramlike reaction.

Nelfinavir
  • Diarrhea

  • Nausea, vomiting

  • Elevations in liver function tests

  • Fatigue

  • High risk of adverse effects; avoid if possible.

  • Diarrhea is very common. It usually can be managed with antidiarrheals such as loperamide and diphenoxylate/atropine.

Ritonavir
(see Pharmacokinetic Enhancers)
Saquinavir
  • Nausea, vomiting, diarrhea

  • Elevations in liver function tests

  • Headache

  • Oral ulcerations

  • Available in tablets and hard-gel capsules.

  • Must be used in combination with low-dose ritonavir.

Tipranavir
  • Nausea, vomiting, diarrhea

  • Elevations in liver function tests

  • Increased total cholesterol and triglycerides

  • Rash

  • Intracranial hemorrhage

  • Must be coadministered with ritonavir; should never be used without ritonavir boosting.

  • Should be taken with food.

  • May cause rash in patients sensitive to or intolerant of sulfonamides.

  • Case reports of intracranial hemorrhage; association between tipranavir and intracranial hemorrhage is not clear.

  • Many drug-drug interactions. Certain drug combinations should be avoided. Consult current information before prescribing.

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Chemokine Coreceptor Antagonists
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Drug Adverse Events Comments
Maraviroc
  • Diarrhea, nausea

  • Elevations in liver function tests, hepatitis

  • Upper respiratory tract infections, cough

  • Fatigue, dizziness, headache

  • Joint pain, muscle pain

  • Many drug-drug interactions; dose adjustment needed with many other antiretrovirals and/or other medications. Consult current information before prescribing.

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Fusion Inhibitors
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Drug Adverse Events Comments
Enfuvirtide
  • Injection site reactions; erythema, cysts, and nodules at injection sites

  • Neutropenia

  • Possible increased frequency of pneumonia

  • Requires extensive patient counseling on injection technique, adherence, and management of possible side effects.

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Pharmacokinetic Enhancers
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Drug Adverse Events Comments
Cobicistat
  • Increased serum creatinine, proteinuria

  • Nausea, diarrhea

  • Headache

  • Cobicistat can inhibit renal tubular secretion of creatinine; clinicians will need to differentiate cobicistat effects from nephrotoxicity.

  • Has significant interactions with many other drugs; consult a reliable drug interaction resource before prescribing.

Ritonavir
  • Adverse effects more likely with higher doses

  • Nausea, vomiting, diarrhea, abdominal pain

  • Elevations in liver function tests

  • Fatigue

  • Circumoral or peripheral numbness

  • Taste perversion

  • Hyperuricemia

  • Has significant interactions with many other medications; consult a reliable drug interaction resource before prescribing.

  • Avoid combining oral solution with metronidazole or disulfiram. Alcohol in the oral solution may cause disulfiramlike reaction.

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