While many are mild and/or transient, others may be intolerable and—in rare cases—lead to life-threatening complications. Some side effects are common with all ARVs—albeit to varying degrees—while others may be confined to certain classes of drugs or individual drug agents.
Although newer ARVs have far fewer side effects compared to older generation ARVs, side effects can still occur.
Central Nervous System Effects
Some ARVs affect the central nervous system (CNS), which is made up of the brain and spinal cord. CNS effects can include a wide range of functions, including:
The ability to see, hear, taste, smell, and feel different sensationsThe ability to think, reason, speak, and form memoriesVoluntary and involuntary functions, such as movement, balance, coordination, as well as regulating the actions of most other body systems, such as blood flow and blood pressure
Though CNS effects are more closely associated with certain older ARVs, mainly Sustiva, they are also present—though to a lesser degree—with non-nucleoside reverse transcriptase inhibitors (NNRTIs) like Edurant and Viramune.
Newer integrase inhibitors can also cause CNS effects. Possible ARV-induced CNS effects include:
Nightmares Dizziness Insomnia Nervousness Lack of concentration Depression Suicidal ideation Psychosis
Liver Toxicity
Hepatotoxicity is the medical term for damage to the liver caused by a medicine, chemical, or supplement, and can be a side effect of some HIV medicines.
The liver helps the body break down certain medicines—including NNRTIs and ARVs—but the process is slower in some people than in others, which can be harmful to the liver. Though rare, hepatotoxicity can, in some cases, lead to liver failure.
Viramune, an older NNRTI, is most strongly linked to hepatotoxicity, but it can also occur with other ARVs like AZT, Sustiva, Selzentry, and all protease inhibitors. People with underlying liver impairment are at the greatest risk.
As liver toxicity is possible with many ARVs, liver function is commonly monitored during treament.
The symptoms of hepatotoxicity include:
RashStomach painNausea and vomitingFatigueDark-colored urineLight-colored bowel movementsJaundice (yellow skin and eyes)Loss of appetiteFever
Kidney Impairment
Renal impairment refers to a situation where a person’s kidneys are unable to perform their function of cleaning and filtering blood. Nephrotoxicity is the adverse effect of substances—including medications—on kidney function.
Fulminant and cholestatic hepatitisHepatic necrosisHepatic failure
Changes in renal function, including those caused by nephrotoxicity, are assessed using clinical markers including:
Glomerular filtration rate (GFR)Blood urea nitrogen (BUN)Serum creatinine (sCr)Urine output
Although, in some cases, nephrotoxicants can cause kidney damage without changing any established clinical marker of renal function. In some cases, renal impairment and nephrotoxicity can get to the point of causing kidney failure.
Sometimes, having a person stop taking the nephrotoxic medication and substituting it with another one can resolve problems with kidney function. But in other cases the damage is permanent.
Renal impairment is most commonly associated with tenofovir disoproxil fumarate (TDF) and is less of a concern with tenofovir alafenamide (TAF), a newer version of the drug.
The newer post-attachment inhibitor Trogarzo is also associated with a risk of kidney damage. Renal function is commonly monitored to avoid kidney injury.
While drug-induced renal impairment and toxicity are frequently asymptomatic—and therefore require lab tests to be done to check a variety of biomarkers—signs and symptoms of kidney damage may include:
Urination changes, such as little or no urine, excessive urination at night, or urination that stops completelyDecreased appetitePersistent hiccupsBreath odor and a metallic taste in the mouthBruising easilyChanges in mental status or moodFatigue or slow sluggish movementsNausea or vomiting that may last for daysNosebleedsHand tremorHigh blood pressureDecreased sensation, especially in the hands or feetFlank pain (between the ribs and hips)Heart murmurSwelling due to the body keeping in fluid (may be seen in the legs, ankles, and feet)Bloody stoolsProlonged bleedingSeizuresShortness of breath
Lactic Acidosis
Lactic acidosis occurs when lactic acid—which is produced when oxygen levels become low in cells within the areas of the body where metabolism takes place—builds up in the bloodstream.
Lactic acidosis was a major, and sometimes potentially life-threatening concern with an older nucleos(t)ide reverse transcriptase inhibitor (NRTI) called Zerit, though it can also occur with AZT and Videx, although the risk is much lower.
There are no signs of symptoms unique to lactic acidosis, and the ones that do occur can vary significantly depending on the cause of the lactic acidosis. But generally speaking, symptoms of lactic acidosis may include:
WeaknessNauseaVomiting
Hyperlipidemia
Certain ARVs can increase lipid levels, leading to high cholesterol and triglycerides. Hyperlipidemia is most commonly associated with Ziagen, AZT, Prezista, Reyataz, Kaletra, and elvitegravir.
Lactic acidosisPancreatitisPeripheral neuropathyLipoatrophy
In most cases, there are no symptoms specific to drug-induced hyperlipidemia. However, because high levels of cholesterol can cause a variety of other health conditions and concerns, it’s important to keep an eye out for those, including:
Symptoms of peripheral artery disease (PAD):
Leg discomfortLeg pain or cramping that occurs when walking and is relieved at rest (intermittent claudication)Pain in the ball of the foot or toes while at rest, as PAD progressesIn more severe forms, painful foot ulcers, blue or black discoloration of the toes, infections, and gangrene
Symptoms of a transient ischemic attack (TIA) or stroke:
Sudden, severe headacheWeakness, numbness, or tingling on one side of your body (one arm and/or leg)Loss of movement of one arm or legPartial vision loss in one eye (often described as pulling down a window shade)Inability to speak clearly or express your thoughts
Symptoms of a heart attack:
Chest pain, which may feel like pressure or squeezing in your chestPain or pressure in your shoulders, arms, neck, jaw, or backShortness of breath
Angina:
Chest pain that happens when your heart muscle can’t get enough oxygen.
Hyperglycemia
Hyperglycemia is when there is too much sugar in the blood because the body has too little insulin or when the body can’t use insulin properly. It is most commonly linked to protease inhibitors—especially Crixivan—and certain NRTIs, like Videx and Zerit. The symptoms of drug-induced hyperglycemia may include:
High blood sugarIncreased thirst and/or hungerBlurred visionFrequent urinationHeadacheFatigue (feeling weak, tired)Weight lossVaginal and skin infectionsSlow-healing cuts and sores
If left untreated in people with type 1 diabetes, hyperglycemia can develop into ketoacidosis: a condition that is a medical emergency and can lead to coma or death. Symptoms of ketoacidosis include:
VomitingDehydrationUnusual fruity smell on the breathDeep labored breathing or hyperventilationRapid heartbeatConfusion and disorientationComaExcessive thirstFrequent urinationNausea and vomitingDehydrationWeakness or fatigue
Lipodystrophy
Lipodystrophy is the abnormal distribution of fat in the body and can be either genetically inherited or acquired. It is strongly linked to older PIs (like Crixivan) and older NRTIs (like AZT, Videx, and Zerit).
Lipodystrophy is largely irreversible once it occurs, and sometimes requires surgery and dermal fillers to correct the abnormalities.
The symptoms of lipodystrophy resulting from HIV medications include:
Gradual loss of subcutaneous fat from the arms, legs, and face. Developing excess fat in the face, neck, upper back, and waist. This can cause a double chin, a hump on the upper back (also referred to as a “buffalo hump”), and expand the circumference of the waist.
Peripheral Neuropathy
Peripheral neuropathy is a disorder of peripheral nerves, and among the most frequent neurological complications of HIV infection, affecting:
Peripheral sensory and motor nervesThoracic nervesCranial nervesAutonomic nerves
As with lipodystrophy, peripheral neuropathy is often difficult to reverse once it occurs.
In addition to being caused by the virus itself, certain HIV drugs can strip the myelin sheath surrounding nerves, also resulting in the condition. Peripheral neuropathy is strongly linked to older NRTIs like Hivid, Zerit, Videx, and lamivudine.
Other drugs used in the treatment of HIV-related disorders can also increase the chance of developing peripheral neuropathy, and include:
Dapsone, used for pneumocystis pneumonia (PCP)Isoniazid, (INH, Nydrazid), used to treat tuberculosisMetronidazole (Flagyl), used to treat amoebic dysentery and microsporidiosisVincristine (Oncovin), used for Kaposi’s sarcoma (KS) and non-Hodgkin’s lymphomaThalidomide, used to treat cancers, wasting syndrome, and severe mouth ulcersEthambutol (Myambutol), used to treat Mycobacterium avium complex (MAC) and other bacterial infections
The symptoms of peripheral neuropathy can include:
Mild-to-severe painBurning in feet and toesNumbness in feet and toesTingling in feet and toesStiffness in feet and toesPrickling in feet and toesLoss of feeling in the toes and soles of the feetPain from nerves affected in the fingers, hands, and wrists (though less common)Pain above the ankles (also relatively uncommon)
Drug Hypersensitivity
Hypersensitivity can occur with any drug, but certain ARVs have a higher potential for it. Ziagen and Selzentry are the two drugs most commonly associated with hypersensitivity reaction (HSR), which in some cases can become life-threatening.
Most cases develop within one to six weeks of starting treatment. The symptoms of drug hypersensitivity can include:
Maculopapular rashes (that include both raised bumps and flat, discolored areas of skin) Erythroderma (widespread redness on the skin, accompanied by scaling, peeling, and flaking of the skin, and potentially, hair loss) Exfoliative dermatitis (a severe inflammation of at least 90% of the skin’s entire surface) Fever Rigors Myalgia (muscle pain) Arthralgia (aching or pain in one or more of the joints in the body)
Though extremely rare, in some cases, drug hypersensitivity can trigger systemic, occasionally life-threatening reactions, which may include anaphylaxis and require emergency medical treatment.
Callout:
A Word From Verywell
Overall, the benefits of antiretroviral therapy invariably outweigh the risks. Taking your HIV medication daily as prescribed provides many benefits. Getting and keeping an undetectable viral load is the best thing you can do to stay healthy. If someone with HIV does experience a side effect, a dose adjustment or drug substitution can, in many cases, resolve the symptoms.
At the same time, this serves as a reminder to always be completely transparent with your healthcare provider about any underlying conditions you may have—especially before starting a new medication. This can help you avoid medications that cause side effects in the first place.
Finally, if you begin taking a new drug and notice that your body and/or brain are feeling different (and not in a good way), bring this up with your healthcare provider. In some cases, it could be a common, harmless side effect of a medication. But in other situations, it may be the indication of something more serious that needs to be addressed immediately.
