Facet Results and Complication of HIV Medication

Antiretroviral drugs (ARVs) have transformed HIV from a life-threatening disease to a chronically managed one. But, as with all drugs, there are certain side effects.

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.

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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 sensations.
  • The ability to think, reason, speak, and form memories.
  • Voluntary 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

Use of Sustiva

Sustiva—the brand name of the NNRTI efavirenz—is commonly avoided in people with clinical depression or psychiatric problems. This is because it can make existing depression worse, including leading to suicidal ideation and/or 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:

  • Rash
  • Stomach pain
  • Nausea and vomiting
  • Fatigue
  • Dark-colored urine
  • Light-colored bowel movements
  • Jaundice (yellow skin and eyes)
  • Loss of appetite
  • Fever

Viramune and People With Liver Problems

Viramune is contraindicated for use in people with liver problems. Severe, life-threatening, and in some cases fatal hepatotoxicity have been reported in patients treated with Viramune. These include:

  • Fulminant and cholestatic hepatitis
  • Hepatic necrosis
  • Hepatic failure

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.

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 completely
  • Decreased appetite
  • Persistent hiccups
  • Breath odor and a metallic taste in the mouth
  • Bruising easily
  • Changes in mental status or mood
  • Fatigue or slow sluggish movements
  • Nausea or vomiting that may last for days
  • Nosebleeds
  • Hand tremor
  • High blood pressure
  • Decreased sensation, especially in the hands or feet
  • Flank pain (between the ribs and hips)
  • Heart murmur
  • Swelling due to the body keeping in fluid (may be seen in the legs, ankles, and feet)
  • Bloody stools
  • Prolonged bleeding
  • Seizures
  • Shortness of breath

TDF and People With Kidney Disease

Tenofovir disoproxil fumarate (TDF), an HIV treatment since 2001, is contraindicated for use in people with kidney disease. Several studies later, we now know that TDF presents a tubular toxicity risk and shouldn’t be used by people with kidney disease.

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:

Zerit Was Discontinued in the United States

Because of the risk of lactic acidosis and other concerns, Zerit was discontinued in the United States in 2020. This followed reports of fatal and nonfatal cases of:

  • Lactic acidosis
  • Pancreatitis
  • Peripheral neuropathy
  • Lipoatrophy

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.

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 discomfort
  • Leg 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 progresses
  • In 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 headache
  • Weakness, numbness, or tingling on one side of your body (one arm and/or leg)
  • Loss of movement of one arm or leg
  • Partial 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 chest
  • Pain or pressure in your shoulders, arms, neck, jaw, or back
  • Shortness 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 sugar
  • Increased thirst and/or hunger
  • Blurred vision
  • Frequent urination
  • Headache
  • Fatigue (feeling weak, tired)
  • Weight loss
  • Vaginal and skin infections
  • Slow-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:

  • Vomiting
  • Dehydration
  • Unusual fruity smell on the breath
  • Deep labored breathing or hyperventilation
  • Rapid heartbeat
  • Confusion and disorientation
  • Coma
  • Excessive thirst
  • Frequent urination
  • Nausea and vomiting
  • Dehydration
  • Weakness or fatigue
  • Unusual fruity smell on the breath
  • Deep labored breathing or hyperventilation
  • Rapid heartbeat
  • Confusion and disorientation
  • Coma

Protease Inhibitor-Induced Hyperglycemia and Type 2 Diabetes

Studies have shown a direct association between PI-induced hyperglycemia and the onset of type 2 diabetes.

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 nerves
  • Thoracic nerves
  • Cranial nerves
  • Autonomic 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 tuberculosis
  • Metronidazole (Flagyl), used to treat amoebic dysentery and microsporidiosis
  • Vincristine (Oncovin), used for Kaposi’s sarcoma (KS) and non-Hodgkin’s lymphoma
  • Thalidomide, used to treat cancers, wasting syndrome, and severe mouth ulcers
  • Ethambutol (Myambutol), used to treat Mycobacterium avium complex (MAC) and other bacterial infections

The symptoms of peripheral neuropathy can include:

  • Mild-to-severe pain
  • Burning in feet and toes
  • Numbness in feet and toes
  • Tingling in feet and toes
  • Stiffness in feet and toes
  • Prickling in feet and toes
  • Loss of feeling in the toes and soles of the feet
  • Pain 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:

HSR and Ziagen

HSR can occur in genetically-susceptible people (with the HLA-B*57:01 allele) who receive Ziagen, and can be life-threatening if not stopped immediately.

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 doctor 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 doctor. 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.

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