Introduction
Like 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.
back to topVariation 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.
back to topDuration 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.
back to topPreparing 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.
back to topReporting 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.
back to topIdentifying 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.
back to topDealing with side effects
There may be several options for dealing with a particular side effect:
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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.
back to topOverview 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.
Bananas aid recovery from diarrhoea
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.
Although it may not be enough to solve the problem, changing diet may reduce the severity of
diarrhoea. Good advice includes:
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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 HIVpositive 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:
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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:
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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:
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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.
Oily fish are good for lipid levels
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
2008
A multi-cohort study involving
33347 patients finds a 90% percent
D:A:D study
increased risk of heart attack with
use of abacavir and a 49%
increased risk with didanosine5
Study analysed the D:A:D findings
and concluded that abacavir, but
SMART/INSIGHT
not didanosine, was associated
with increased risk of heart attack6
No evidence for increased risk
Evidence for increased risk
GSK statement
No evidence for increased risk
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
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
Allrt
Study of 10,931 patients found an
US Veteran Affairs increased risk of cardiovascular
Department
events associated with recent use
of abacavir9
26 randomised clinical trials concluded
that there was no increased risk of
heart attack with abacavir10
FDA
Other side effects
Abacavir hypersensitivity reaction
Associated
drugs
How frequent
Symptoms
Suggestions
Medical
treatments
Abacavir
Around 8%, but less if patients are screened
May include rash, fever, severe tiredness, muscle aches, diarrhoea, nausea,
vomiting, stomach pain, sore throat, general ill feeling
 Seek immediate medical attention
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Switch drugs
Appetite loss (anorexia)
Associated
drugs
Abacavir
Nausea, changes in taste perception (linked to some protease inhibitors), other
infections, low hormone levels, depression, nutrient deficiencies
How frequent Common
 Eat several small meals instead of a few large meals
 Use different flavourings
Suggestions
 Drink smoothies, soups or supplement drinks
Other causes
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Medical
treatments
Treatments for non-drug-related causes
Appetite stimulants
Central nervous system effects
Efavirenz
Mild effects are common
Dizziness, mood changes, depression, anxiety, paranoia
 Wait for improvement – may get better after a few weeks
 Adjust timing of efavirenz dosing
 Avoid alcohol and recreational drugs
Associated drugs
How frequent
Symptoms
Suggestions
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Medical treatments
Psychotherapy or antidepressants for depression
Fatigue
Associated
drugs
Other causes
How frequent
Suggestions
Various
Insomnia, HIV, other infections, other drugs, low hormone levels, stress,
depression, anaemia, nutrient deficiencies
Common
 Get tested for anaemia
 Eat a good diet
 Take moderate exercise
 Cut down on alcohol, recreational drugs and smoking
Medical
treatments
Associated drugs
Other causes
How frequent
Suggestions
Medical treatments
Associated drugs
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Treatments for non-drug-related causes
Possibly psychostimulants
Insomnia
Various but especially efavirenz
Stress, anxiety, depression, pain, caffeine
Common
 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
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Possibly sleeping pills, but only as a temporary solution
Insulin resistance and diabetes
Protease inhibitors
How frequent
Symptoms
Suggestions
3-5%
Fatigue, weakness, frequent urination, increased thirst
 Take moderate exercise
 Lose weight if obese
 Consult a dietician and follow their advice
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Medical treatments
Associated drugs
Other causes
How frequent
Symptoms
Suggestions
Insulin injections
Various medications
Kidney damage (nephrotoxicity)
Tenofovir
HIV
Rare
Fatigue, weakness, frequent urination, increased thirst
Often no symptoms; detected through laboratory monitoring
 Seek medical advice
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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
Nausea and vomiting, abdominal pain, tiredness, shortness of breath, abnormal
Symptoms
heart beat, weight loss
 Seek immediate medical attention
Suggestions
Medical
treatments
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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
General: Fatigue, loss of appetite, abdominal pain
Symptoms
Jaundice: Yellow skin and whites of the eyes, dark urine, pale stools
 Seek medical advice
Suggestions
Medical
treatments
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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
 Seek immediate medical attention
Suggestions
Medical treatments
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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
Begins with numbness and pins and needles in hands or feet
Symptoms
Can become very painful and eventually disabling
 Try cold water and massage
 Minimise strain on hands and feet
Suggestions
 Enquire about reducing dosage
Medical
treatments
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Painkillers
Alternative treatments such as acupuncture (unproven)
Switching drugs should stop it getting worse but may not reverse
symptoms