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Antiretroviral Drugs Side Effects

Introduction

Antiretroviral drugsLike most medicines, antiretroviral drugs can cause side effects. These unwanted effects are often mild, but sometimes they are more serious and can have a major impact on health or quality of life. On rare occasions, side effects can be life threatening.

Once started, antiretroviral treatment must be taken every day for life. Every missed dose increases the risk that the drugs will stop working. It is therefore vital that people receiving antiretroviral treatment get all the help they need to minimise the impact of side effects. Often there are several ways to lessen the harm, either by treating the side effects or by switching to alternative antiretroviral drugs.

Variation in side effects

Antiretroviral drugs differ in how commonly they cause particular side effects. For example, efavirenz is the drug most associated with psychiatric symptoms, while protease inhibitors are more likely to raise levels of cholesterol and triglycerides. This should be considered when deciding which drugs to take.

Side effects vary from person to person and it is impossible to predict exactly how each individual will be affected. Some people take antiretroviral treatment for years with few problems, while others find the same drugs intolerable. Nevertheless some characteristics and pre-existing conditions (such as high blood pressure or hepatitis infection) are known to increase the risk from certain side effects. Doctors should assess these factors before advising patients on which drugs to choose.

Duration of side effects

Some side effects appear shortly after starting an antiretroviral drug and disappear within a few weeks as the body gets used to the new chemicals. This is often the case with nausea, diarrhoea and headache, for example.

Unfortunately other side effects – such as peripheral neuropathy (nerve damage) and lipodystrophy (fat redistribution) – tend to worsen over time and may never go away. Also some problems may not emerge until months or even years after treatment is started.

Preparing to start treatment

Those preparing to take antiretroviral treatment for the first time, or about to switch drugs, are well advised to learn a little about the most commonly associated side effects. This should help them deal with problems as soon as they arise.

Patients should also know how to spot the warning signs of more serious side effects that may require immediate intervention.

Reporting side effects

Because side effects are unpredictable, may occur at any time, and can be very serious, it is essential that all symptoms be reported during appointments with a doctor. Severe or unexpected events should be reported immediately.

Keeping a side effects diary is a good way to keep track of when symptoms occur, how often and how severely. If side effects are affecting quality of life or treatment adherence then this too should be reported.

Identifying the cause

Most side effects are not uniquely associated with a particular drug, and sometimes it can be difficult to identify the cause. HIV itself is capable of producing many of the symptoms that also occur as drug side effects. Other possible causes include opportunistic infections, stress, diet, and non-HIV drugs.

“Patients should make sure their doctors are aware of all drugs they are taking”

Patients should make sure their doctors are aware of all drugs they are taking. This means not only pharmaceuticals but also recreational drugs and complementary and alternative therapies. It may be that a side effect is due to one of these other substances, either directly or because of an interaction with the antiretroviral medication. The more information is shared with a doctor, the better equipped they will be to help.

Older people living with HIV may experience signs of ageing that could resemble certain side effects. For example, when people get older they might be more susceptible to increased fat in the abdomen, which could look similar to the changes that are caused by lipodystrophy.

Dealing with side effects

There may be several options for dealing with a particular side effect:

  • Wait for things to improve – especially if in the first few weeks of treatment
  • Address other possible contributing factors, such as diet, smoking or exercise
  • Change how the drug is taken (e.g. time of day, dosage, with or without food)
  • Try treating the side effect
  • Change one or more antiretroviral drugs

Switching drugs is often an effective way to reduce or eliminate a side effect when all other approaches have failed. If the viral load is undetectable then it is usually possible to switch only one drug without affecting treatment effectiveness or future treatment options. Otherwise, the entire combination may have to be changed.

Switching drugs is not without risks. As already mentioned, it can be difficult to identify the cause of a particular set of symptoms, and it may turn out that the rejected drug or drugs weren’t to blame after all. There is also a chance that the new medication may cause even worse side effects, perhaps forcing another switch. Changing drugs repeatedly will narrow future treatment options. It is important to weigh the possible risks and benefits before deciding on this course of action.

It is never a good idea to stop treatment without first consulting a doctor, as this may cause HIV to develop drug resistance.

For information on dealing with pain directly see our AIDS and pain page.

Overview of antiretroviral drug side effects

Some of the side effects of antiretroviral drugs are described below, beginning with five of the most notable. This is not a complete list.

Diarrhoea

Diarrhoea is a common side effect of many antiretroviral drugs – especially protease inhibitors. A study review has found that 60 percent of people living with HIV report diarrhoea.1 Other possible causes include HIV, the effect that HIV has on the gastrointestinal tract, other infections and antibiotics.2  Sometimes an antiretroviral drug causes diarrhoea for only the first few weeks; in other cases this side effect lasts for as long as the drug is taken.

The severity of diarrhoea also varies. While even occasional attacks may be inconvenient and embarrassing, persistent diarrhoea can also lead to dehydration, poor absorption of nutrients and drugs, weight loss and fatigue.

Drinking plenty of fluids and replacing electrolytes will reduce the risk of dehydration. Electrolytes – such as potassium, sodium and magnesium ions – are essential to health and are depleted by diarrhoea. Ways of replacing electrolytes include oral rehydration salts (available from pharmacies), sports rehydration drinks (such as Gatorade or Powerade, though the high sugar content may worsen diarrhoea), diluted fruit juices, soups, and homemade rehydration mixtures (8 level teaspoons of sugar and 1 level teaspoon of table salt per litre of water). Eating bananas, potatoes, fish or chicken will help to replace potassium.Eating bananas helps recovery from diarrhoea, a common side effect of antiretroviral treatment

Although it may not be enough to solve the problem, changing diet may reduce the severity of diarrhoea. Good advice includes:

  • Eat less insoluble fibre (raw vegetables, fruit skins, wholegrain bread or cereal, seeds and nuts)
  • Eat more soluble fibre (white rice, pasta, oat bran tablets, psyllium/isphagula)
  • Cut down on caffeine, alcohol and the sweetener sorbitol
  • Avoid greasy, fatty, spicy and sugary foods
  • Consider reducing dairy products in case of lactose intolerance
  • Consult a dietician

There is currently no recommended therapy for non-infectious forms of diarrhoea in HIV-positive people.3 Over-the-counter medicines such as Imodium (loperamide), Lomotil (diphenoxylate and atropine) and calcium supplements are sometimes all that is needed to control diarrhoea. If these fail then doctors can prescribe stronger treatments, which may have to be injected. Sometimes nothing works, and changing drugs may be the best option.

Nausea and vomiting

Almost all antiretroviral drugs, as well as many other medications, can cause nausea (feeling sick) and vomiting, especially during the first few weeks of treatment. Although this side effect can reduce appetite, it is important to keep eating when possible, and to replace lost fluids and electrolytes (as with diarrhoea). The following measures may help:

  • Eat several small meals instead of a few large meals
  • Avoid spicy, greasy and rich foods; choose bland foods
  • Eat cold rather than hot meals
  • Don’t drink with a meal or soon after
  • Avoid alcohol, aspirin and smoking
  • Avoid cooking smells

Some antiretroviral drugs can be taken with food, and doing so may lessen their harmful effects. It may also be possible to alter drug dosage or frequency.

Various treatments, known as anti-emetics, are available for nausea and vomiting, some of which do not require a prescription. There is some evidence that ginger and peppermint may help against nausea.

If nausea and vomiting are severe, or occur with other symptoms such as dizziness, thirst, fever, muscle pain, diarrhoea, headache or jaundice, then this may indicate a more serious problem such as lactic acidiosis or pancreatitis. In this case medical attention should be sought as soon as possible.

Rash

Rashes often appear as a side effect of antiretroviral treatment. These may be itchy but are usually harmless and short-lived. However, severe rashes can occur with nevirapine, and more rarely with some other drugs. Any rash occurring during the first few weeks of treatment should be reported to a doctor immediately, as should any rash accompanied by fever, blistering, facial swelling or aches. A rash occurring with abacavir may indicate a very dangerous hypersensitivity reaction, as described later in this page.

Tips for coping with rashes include:

  • Avoiding hot showers or baths
  • Using milder toiletries and laundry detergents
  • Wearing cool fibres such as cotton, and avoiding wool
  • Humidifying the air
  • Trying moisturisers/emollients or calamine lotion

Antihistamine tablets can sooth rashes and are generally available without a prescription. However, because these may interact with antiretroviral medications, patients should check with their doctors before using them. More severe skin problems may be treated with steroids.

Lipodystrophy

Lipodystrophy involves losing or gaining body fat, often in ways that can be disfiguring and stigmatising. Three main patterns are seen:

  • Losing fat on the face, arms, legs and buttocks, resulting in sunken cheeks, prominent veins on the limbs, and shrunken buttocks.
  • Gaining fat deep within the abdomen, between the shoulder blades, or on the breasts.
  • A mixture of fat gain and fat loss.

Although lipodystrophy sometimes affects people with HIV who have not taken any antiretroviral drugs, it occurs more often among those receiving treatment. The condition is among the most common long-term side effects of combinations of drugs from the NRTI and protease inhibitor classes. It is particularly associated with stavudine, and to a lesser extent zidovudine. The precise causes of lipodystrophy remain unknown.

“The treatments for lipodystrophy are sadly limited”

The treatments for lipodystrophy are sadly limited. Changing diet seems to make no significant difference, though resistance exercise (such as weight lifting) may improve the appearance of limbs by building muscle to compensate for lost fat. Any form of exercise will burn fat, which may make some parts of the body look better and others worse, depending on how fat has been redistributed. Aerobic exercise (such as running or swimming) tends to have more effect on the fat just below the skin than on the deep fat gained through lipodystrophy.

Doctors have tried using various medications, including human growth hormone, to treat lipodystrophy, but few have proved effective, and most have significant side effects. For people who have lost fat from the face, one option is injections of polylactic acid. This chemical (also known as New Fill or Sculptra) improves facial appearance by thickening the skin.

Switching antiretroviral treatment should stop the symptoms getting worse, but is unlikely to lead to much improvement once the condition has advanced.

Lipid abnormalities and the heart

Lipid abnormalities are another common side effect of some antiretroviral drugs – particularly protease inhibitors – and are often seen in people who also have lipodystrophy. Lipids are molecules of fat, cholesterol and related chemicals that have important roles in the body. Many factors including diet, smoking and exercise can affect the balance of these chemicals in the blood. Abnormal lipid levels can be harmful to health.

HIV positive people taking antiretroviral treatment commonly have high levels of a lipid called LDL cholesterol, low levels of HDL cholesterol, and high levels of triglyceride in the blood. Among HIV negative people such lipid abnormalities have been linked to greater risks of heart disease, stroke and diabetes.

The first steps in treating lipid abnormalities should be related to diet and lifestyle. General recommendations include giving up smoking, taking more exercise, cutting calories, eating less fat, and consuming more fibre and omega-3 fatty acids (found in oily fish and flaxseed). However, people living with HIV should seek expert advice on applying these guidelines. For example, cutting calories may jeopardise attempts to build muscle, while eating less fat is not necessarily a good idea for people taking certain protease inhibitors that require fatty foods to aid absorption.

Yet although diet and lifestyle changes should always be part of the strategy, they are often inadequate to correct the problem. Doctors may prescribe medications such as statins and fibrates to improve lipid levels, or they may advise switching treatment.

In 2008, a large investigation called the D:A:D study4 reported that use of the NRTI abacavir was associated with a higher risk of myocardial infarction (also known as heart attack) compared to other drugs in the same class. Since then, some studies have supported the findings of the D:A:D study while others have contested these findings and found no increased risk of heart attack with abacavir. The table below shows the findings of the relevant studies and trials that have taken place so far:

Abacavir and increased risk of heart attack

  Evidence for increased risk No evidence for increased risk
2008    
D:A:D study A multi-cohort study involving 33347 patients finds a 90% percent increased risk of heart attack with use of abacavir and a 49% increased risk with didanosine5  
SMART/INSIGHT Study analysed the D:A:D findings and concluded that abacavir, but not didanosine, was associated with increased risk of heart attack6  
GSK statement   GSK's Internal databases of 54 clinical trials with more than 14,000 patients, over 9,600 of whom were on abacavir show no increased risk of heart attack7
2011    
Allrt   Study of 5056 patients found no increased risk of heart attack from either short or long term use of abacavir. Traditional risk factors, such as smoking and older age were instead attributed to increased risk.8
US Veteran Affairs Department Study of 10,931 patients found an increased risk of cardiovascular events associated with recent use of abacavir9  
FDA   26 randomised clinical trials concluded that there was no increased risk of heart attack with abacavir10

Other side effects

Abacavir hypersensitivity reaction
Associated drugs Abacavir
How frequent Around 8%, but less if patients are screened
Symptoms May include rash, fever, severe tiredness, muscle aches, diarrhoea, nausea, vomiting, stomach pain, sore throat, general ill feeling
Suggestions
  • Seek immediate medical attention
Medical treatments
  • Switch drugs
Appetite loss
Associated drugs Abacavir
Other causes Nausea, changes in taste perception (linked to some protease inhibitors), other infections, low hormone levels, depression, nutrient deficiencies
How frequent Common
Suggestions
  • Eat several small meals instead of a few large meals
  • Use different flavourings
  • Drink smoothies, soups or supplement drinks
Medical treatments
  • Treatments for non-drug-related causes
  • Appetite stimulants
Central nervous system effects
Associated drugs Efavirenz
How frequent Mild effects are common
Symptoms Dizziness, mood changes, depression, anxiety, paranoia
Suggestions
  • Wait for improvement – may get better after a few weeks
  • Adjust timing of efavirenz dosing
  • Avoid alcohol and recreational drugs
Medical treatments
  • Psychotherapy or antidepressants for depression
Fatigue
Associated drugs Various
Other causes Insomnia, HIV, other infections, other drugs, low hormone levels, stress, depression, anaemia, nutrient deficiencies
How frequent Common
Suggestions
  • Get tested for anaemia
  • Eat a good diet
  • Take moderate exercise
  • Cut down on alcohol, recreational drugs and smoking
Medical treatments
  • Treatments for non-drug-related causes
  • Possibly psychostimulants
Insomnia
Associated drugs Various but especially efavirenz
Other causes Stress, anxiety, depression, pain, caffeine
How frequent Common
Suggestions
  • Avoid caffeine and other stimulants
  • Take moderate exercise
  • Stick to a regular sleeping pattern; avoid napping
  • Ensure bedroom is comfortable, relaxing and quiet
  • Drink herbal teas, and drink a warm, milky drink before bedtime
Medical treatments
  • Possibly sleeping pills, but only as a temporary solution
Insulin resistance and diabetes
Associated drugs Protease inhibitors
How frequent 3-5%
Symptoms Fatigue, weakness, frequent urination, increased thirst
Suggestions
  • Take moderate exercise
  • Lose weight if obese
  • Consult a dietician and follow their advice
Medical treatments
  • Insulin injections
  • Various medications
Kidney damage (nephrotoxicity)
Associated drugs Tenofovir
Other causes HIV
How frequent Rare
Symptoms Fatigue, weakness, frequent urination, increased thirst
Often no symptoms; detected through laboratory monitoring
Suggestions
  • Seek medical advice. It is thought that taking ART improves renal (kidney) function, offsetting this type of side effect from tenofovir
Medical treatments
  • Usually reversible by switching drugs
  • In worst cases, requires dialysis or kidney transplant
Lactic acidiosis
Associated drugs NRTIs, especially stavudine and didanosine
How frequent Rare
Symptoms Nausea and vomiting, abdominal pain, tiredness, shortness of breath, abnormal heart beat, weight loss
Suggestions
  • Seek immediate medical attention
Medical treatments
  • May require hospitalisation
  • Possibly micronutrient supplements
  • Usually best to switch drugs
Liver damage (hepatotoxicity)
Associated drugs Various but especially nevirapine and ritonavir
Other causes Viral hepatitis, alcohol, other drugs
How frequent Mild effects are common; severe cases are rare
Symptoms General: Fatigue, loss of appetite, abdominal pain
Jaundice: Yellow skin and whites of the eyes, dark urine, pale stools
Suggestions
  • Seek medical advice
Medical treatments
  • Either wait for improvement under frequent monitoring or switch drugs
Pancreas damage (pancreatitis)
Associated drugs Stavudine, didanosine
Other causes Alcohol, other drugs, infections
How frequent Rare
Symptoms Nausea and vomiting, abdominal pain
Suggestions
  • Seek immediate medical attention
Medical treatments
  • May require hospitalisation
  • Painkillers
  • Usually best to switch drugs
Peripheral neuropathy (nerve damage)
Associated drugs Stavudine, didanosine, lamivudine
Other causes HIV, diabetes, vitamin deficiencies
How frequent Common with stavudine
Symptoms Begins with numbness and pins and needles in hands or feet
Can become very painful and eventually disabling
Suggestions
  • Try cold water and massage
  • Minimise strain on hands and feet
  • Enquire about reducing dosage
Medical treatments
  • Painkillers
  • Alternative treatments such as acupuncture (unproven)
  • Switching drugs should stop it getting worse but may not reverse symptoms

 

References

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