Patients who use topical antivirals rarely experience side effects. However, side effects that may occur in rare circumstances include burning and stinging, headache, itching (pruritus), mild pain, nausea, skin symptoms such as rash or flaking, and inflammation of the vulva (vulvitis).

Most patients who take systemic antivirals to treat conditions other than human immunodeficiency virus (HIV) do not experience side effects. However, in some patients, systemic antivirals may cause symptoms such as diarrhea, headache, nausea and vomiting. Patients who receive these medications intravenously may also experience inflammation of a vein (phlebitis) and inflammation at the insertion site. Intravenous administration can also result in impairment of the kidneys that may be reversed upon cessation of using the drug.

Systemic antivirals used to treat HIV may cause side effects such as anorexia (loss of appetite), diarrhea, fever, headache, insomnia, gastrointestinal pain, malaise (general ill feeling), myalgia (muscular pain or tenderness), rash, sleeplessness and nausea. In addition, some patients may experience more significant side effects such as bone marrow suppression, hepatic (liver) toxicity, pruritus, pancreatitis (inflammation of the pancreas), oral and esophageal ulcers, cardiomyopathy (disease or disorder of the heart muscle) or peripheral neuropathy (degenerative state of the peripheral nerves).