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HIV treatment combinations and their side-effects

The likelihood of having a side-effect

Side-effects are often described in the following categories:

  • Very common. This means that more than one in ten people taking the medicine are likely to have the side-effect.
  • Common. This means that between one in ten and one in 100 people are affected.
  • Uncommon. This means that between one in 100 and one in 1000 people are affected.
  • Rare. This means that between one in 1000 and one in 10,000 people are affected.
  • Very rare. This means that fewer than one in 10,000 people are affected.
  • Not known. This means that it’s not been possible to estimate the number of people affected.

In this booklet, we list the very common or common side-effects for individual drugs. We have only included the uncommon, rare or very rare side-effects if they are potentially dangerous.

Starting treatment for the first time?

The drugs recommended for people starting HIV treatment for the first time generally have few side-effects.

Because of this, it’s less common than it used to be for people to have to change their HIV treatment because of side-effects. Many people will probably be able to take the currently available first-choice anti-HIV drugs safely for a long time. However, some people do change treatment because of side-effects, so your healthcare team will be used to discussing these sorts of problems and looking at alternative drug choices.

Remember, if you experience any side-effects, mention them at your clinic. If a side-effect persists, it’s nearly always possible to do something about it.

You can read BHIVA’s guidelines for HIV treatment on its website: www.bhiva.org 

Recommended first HIV treatment combination

When you discuss starting HIV treatment with your healthcare team, they will talk to you about the known side-effects of each drug. Make sure you tell them about any concerns you have; they should take these into account in helping you choose the most suitable treatment combination for you.

In the UK, if you are starting HIV treatment for the first time, the recommended treatment is a combination of three drugs. The treatment guidelines recommend that, for most people, this includes tenofovir and emtricitabine (Truvada). These drugs are from the nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) class and would be taken with one of the following as a third drug in the combination:

  • atazanavir (Reyataz). This is a drug from the protease inhibitor class. It has its anti-HIV effect boosted by taking it with a small dose of a second protease inhibitor called ritonavir (Norvir).

or

  • darunavir (Prezista), boosted with ritonavir. Darunavir is also a protease inhibitor.

or

  • dolutegravir (Tivicay). Dolutegravir is an integrase inhibitor.

or

  • elvitegravir, boosted by cobicistat (Stribild). This is an integrase inhibitor.

or

  • raltegravir (Isentress). This is an integrase inhibitor.

or

  • rilpivirine (Edurant). This is a non-nucleoside reverse transcriptase inhibitor (NNRTI).

For some people, efavirenz (Sustiva) will be a suitable third drug in the combination, but this is less commonly used nowadays. This is an NNRTI. An alternative to tenofovir and emtricitabine would be abacavir and lamivudine.

Cost permitting, you may be offered your treatment in a single pill, once a day:

  • Tenofovir disoproxil, emtricitabine and rilpivirine are available in a fixed-dose combination tablet called Eviplera.
  • Dolutegravir, abacavir and lamivudine come in a fixed-dose combination tablet called Triumeq.
  • Odefsey is a fixed-dose tablet combining rilpivirine, emtricitabine and tenofovir alafenamide.
  • Stribild is a fixed-dose tablet combining elvitegravir, emtricitabine and tenofovir disoproxil, along with cobicistat.
  • Genvoya is a fixed-dose tablet combining elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide.
  • Tenofovir disoproxil, emtricitabine and efavirenz are available in a fixed-dose combination tablet called Atripla.

You can find out more about these drugs in the NAM booklet Anti-HIV drugs.

Although these drugs are very effective and generally safe, they can still cause side-effects. Details of these are provided below. You can find more information on the most common side-effects in the section Common side-effects.

Truvada (emtricitabine and tenofovir disoproxil)

Both drugs in Truvada are usually well tolerated. But they can cause diarrhoea, nausea and vomiting. Other very common or common side-effects of both are headache, stomach pain, dizziness, rash and a feeling of weakness.

Other common side-effects of emtricitabine include insomnia (difficulty sleeping) and abnormal dreams, neutropenia (lowered white blood cells), raised liver and pancreatic enzymes, raised levels of the enzyme creatine kinase, heartburn, raised blood sugar and triglycerides (blood fats), and an allergic reaction. Emtricitabine can cause changes in the colour of the skin, particularly in people of non-white race. You should talk to your doctor if this happens to discuss your treatment options. An uncommon side-effect of emtricitabine is anaemia.

Other common side-effects of tenofovir include flatulence, low blood phosphate levels, raised liver enzymes, tiredness and bloating.

Kidney problems can be a rare side-effect of tenofovir, particularly for people who are taking other medicines that affect the kidneys, or for those who have other risk factors for kidney disease, such as high blood pressure or diabetes. Your regular HIV monitoring will include tests to check the health of your kidneys.

More rarely, there is a long-term risk of developing bone problems as a result of treatment with tenofovir. Your regular HIV monitoring will include blood tests to check levels of minerals to make sure that you are not at risk of this side-effect.

There is now a newer formulation of tenofovir (tenofovir alafenamide, or TAF), which may be suitable for people with bone or kidney issues, or people who experienced bone or kidney problems with tenofovir disoproxil (TDF). There is a fixed-dose combination of emtricitabine and TAF available, called Descovy.

Liver problems are a rare side-effect of tenofovir, including hepatitis (liver inflammation).

Atazanavir (Reyataz)

Generally, people tolerate atazanavir well.

Very common or common side-effects: Nausea, diarrhoea, rash, abdominal pain, headache, vomiting, heartburn and tiredness.

A common side-effect of atazanavir is hyperbilirubinaemia, or raised bilirubin levels. Bilirubin is a waste product produced by the liver during the breakdown of old red blood cells. If levels of bilirubin increase this can cause jaundice – yellowing of the skin and whites of the eyes. This is not dangerous, but some people find it distressing.

Talk to your doctor at your routine HIV clinic appointment if you notice a yellowing of your skin or eyes. However, if there is yellowing, and you also feel sick, vomit, have diarrhoea, have stomach pain, or feel generally unwell, you should see a doctor immediately. These could be signs of liver inflammation (hepatitis), which needs immediate monitoring and treatment.

Uncommon or rare side-effects: Kidney stones, gallstones, depression, anxiety, weight gain or loss and changes in appetite, muscle weakness, abnormal liver function, changes in heart rhythm. If you have an existing heart condition, or are on other treatments that can affect heart function, your heart function will be regularly monitored. Rarely, atazanavir can cause a hypersensitivity (allergic) reaction, including a severe rash called Stevens Johnson syndrome. If you develop a rash with other symptoms, such as a fever, seek medical advice.

Atazanavir is not recommended for people with reduced kidney function who need dialysis. Your doctor will test your kidney function before prescribing it, but it is important to tell them about any kidney problems you have or have had in the past. 

Unlike some other anti-HIV drugs, atazanavir is less likely to increase lipid (blood fat) levels, so may be a good option for people with high cholesterol or other risk factors for heart disease.

Darunavir (Prezista)

Generally, people tolerate darunavir well. It's important it's taken with food.

Very common or common side-effects: Diarrhoea, vomiting, nausea, abdominal pain, increased blood amylase, heartburn, flatulence, bloating, headache, peripheral neuropathy (damage to the nerves of the hands and/or feet), dizziness, insomnia (difficulty sleeping), raised lipid levels, diabetes, raised liver and pancreatic enzymes, a feeling of loss of strength, tiredness, rash. A rash is more likely if it is taken in combination with raltegravir.

Uncommon side-effects, rare or very rare side-effects: Abnormal liver function, abnormal kidney function, changes in heart rhythm, changes in blood count, changes in appetite, gout (a build-up of uric acid crystals in the joints), depression, disturbed sleep.

Rarely, darunavir can cause a hypersensitivity (allergic) reaction, including a severe rash called Stevens Johnson syndrome. If you develop a rash with other symptoms, such as a fever, seek medical advice.

Dolutegravir (Tivicay, also in Triumeq)

Generally, dolutegravir causes relatively few side-effects compared to other anti-HIV drugs. However, some people have had to stop treatment with it because of side-effects affecting the central nervous system. These are more common in women, people over 60 and people starting abacavir at the same time as dolutegravir.

Very common or common side-effects: Nausea, diarrhoea, headache, rash, itching, vomiting, stomach pain, insomnia (difficulty sleeping), dizziness, abnormal dreams, fatigue (tiredness), flatulence, increase in liver enzymes, increase in creatine phosphokinase (enzymes produced in the muscles). 

Uncommon side-effects, rare or very rare side-effects: Hepatitis, severe depression. Rarely, dolutegravir can cause a hypersensitivity (allergic) reaction. If you develop a rash with other symptoms, such as a fever, seek medical advice.

Elvitegrevir (Vitekta, also in Genvoya, Stribild)

Generally, people tolerate elvitegravir well. It's important it's taken with food.

Common side-effects: Stomach pain, vomiting, rash, headache, diarrhoea, nausea, fatigue (tiredness).

Uncommon and rare side-effects include: Insomnia (difficulty sleeping), problems with digestion (dyspepsia), feeling bloated, flatulence, dizziness, tingling, abnormal taste. Depression and suicidal thoughts are also uncommon side-effects, affecting people who have pre-existing mental health problems.

Raltegravir (Isentress)

Generally, people tolerate raltegravir well.

Very common and common side-effects: Decreased appetite, headache, insomnia (difficulty sleeping), abnormal dreams, depression, dizziness, vertigo (feeling that you are spinning, or your surroundings are moving), bloating, stomach pain, flatulence, nausea, vomiting, diarrhoea, indigestion, rash, weakness and restlessness, tiredness, fever, raised liver and pancreatic enzymes, raised blood fats (these side-effects would be identified through routine blood tests).

Uncommon side-effects: Dry mouth, shingles, anaemia (low red blood cells) and changes in blood count, iron deficiency, mood changes, disturbed sleep, changes in vision, abnormal kidney function, hepatitis.

In uncommon cases, raltegravir has been known to cause a hypersensitivity (allergic) reaction, including a severe rash called Stevens Johnson syndrome. If you develop a rash with other symptoms, such as a fever, seek medical advice.

Unlike some other anti-HIV drugs, raltegravir is less likely to increase lipid (blood fat) levels, so may be a good option for people with high cholesterol or other risk factors for heart disease.

Rilpivirine (Edurant, also in Eviplera)

Generally, people tolerate rilpivirine well. It’s important it’s taken with food.

Very common or common side-effects: Insomnia (difficulty sleeping), tiredness, drowsiness, headache, nausea, rash, changes in liver and pancreas function, changes in blood counts, increases in blood fats (cholesterol and triglycerides), lack of appetite, depression, dizziness, stomach ache, vomiting, dry mouth.

Efavirenz (Sustiva)

Many people have side-effects in the first few weeks of taking efavirenz, but these often go away fairly quickly. 

Very common or common side-effects: Rash, dizziness, headache, diarrhoea, nausea, vomiting, tiredness, stomach ache, raised triglycerides (blood fats), raised liver enzymes.

Efavirenz can cause a feeling of being ‘out of sorts’, confusion, impaired concentration, sleep disturbance and abnormal dreams. Mental health problems including depression, anxiety and low mood have also been reported as side-effects of efavirenz.

These side-effects are often most noticeable in the first few weeks after treatment with efavirenz is started and then lessen or even go away completely. However, a small number of people experience longer-term or more serious sleep and mood problems due to treatment with efavirenz and some people need to stop taking the drug because of these.

If you do experience side-effects caused by efavirenz, discuss these with your doctor. There may be a number of options available to you to help reduce these side-effects. One simple step you can take is to avoid taking efavirenz with a high-fat meal as this will increase the level of the drug in your body and can increase the side-effects. You could do this by taking it on an empty stomach or at least two hours after food. Taking it an hour or so before bed means that the drug level should be highest while you are asleep.

If you have a history of mental health problems, efavirenz might not be a good choice of treatment and you may want to talk about other treatment options with your doctor.

Uncommon side-effects: Liver problems, pancreatitis. An uncommon side-effect of efavirenz is a hypersensitivity (allergic) reaction, including a severe rash called Stevens Johnson syndrome. If you develop a rash with other symptoms, such as a fever, seek medical advice.

Rarely, people experience serious mental health problems such as psychosis or delusions; this seems to be more likely if you have had mental health issues in the past. If you are worried about your mood or behaviour, bear in mind changes in these could be linked to efavirenz. Talk to your doctor about your concerns.

Other options if you are starting treatment

Your doctor may suggest you start treatment on a different drug combination to the ones described above.

There may be reasons why one of the combinations recommended for starting HIV treatment is not suitable for you. This could be because of possible interactions with other drugs you are taking, or because the type of HIV you have is resistant to one or more drugs. Or it could be because you want to avoid certain side-effects.

In some cases, if your doctor thinks it will work as well for you, they may suggest you start on a combination that costs less for the NHS to buy. Your doctor will only do this if they also think this combination will work for you.

There are some alternative combinations recommended for people starting HIV treatment for the first time.

An alternative to tenofovir and emtricitabine is the combination drug Kivexa (lamivudine and abacavir). An alternative choice for a third drug in the combination is Kaletra, the protease inhibitor lopinavir, boosted with ritonavir, taken in two pills containing the combined drugs.

You can find out more about these drugs in the NAM booklet Anti-HIV drugs.

Although these drugs are effective and generally safe, they can still cause side-effects. Details of these are provided below. You can find more information in the section on Common side-effects.

Kivexa (lamivudine and abacavir)

Generally, people tolerate Kivexa well.

Very common and common side-effects: Both abacavir and lamivudine can cause rash, fever, fatigue (tiredness), headache, nausea, vomiting and diarrhoea. Very common or common side-effects of lamivudine include cough, nasal symptoms, stomach ache, hair loss, insomnia (difficulty sleeping) and joint pain. A common side-effect of abacavir is loss of appetite.

These side-effects are usually quite mild and lessen or go away completely after a few weeks of treatment. Your doctor can also give you other medicines to control some of these side-effects if you need them. See the Common side-effects section for more information on how to manage these.

Rare and very rare side-effects: Rarely, lamivudine can cause liver damage (hepatitis), swelling under the skin and muscle weakness and pancreatitis.

Very rarely, abacavir can cause a hypersensitivity (allergic) reaction, including a severe rash called Stevens Johnson syndrome. If you develop a rash with other symptoms, such as a fever, seek medical advice.

Some (but not all) research has linked abacavir to an increased risk of heart attack, particularly for people who have other risk factors for heart disease. Because of this, abacavir is not recommended for people who have risk factors for heart disease, if a suitable alternative is available.

Kaletra (lopinavir/ritonavir)

Very common or common side-effects: Respiratory tract infections (infections of the sinuses, throat, airways or lungs), skin infections, changes in blood sugars, including diabetes, swollen glands, anaemia and other blood changes, raised blood pressure, anxiety, dizziness, insomnia (difficulty sleeping), headache, nausea, vomiting, diarrhoea, stomach pain and bloating, decreased appetite, muscle weakness, fatigue (tiredness), weakness, muscle pain, heartburn, rash, raised liver enzymes and liver toxicity, erectile dysfunction, menstrual changes (heavy periods or missing periods).

Uncommon and rare side-effects: Increased appetite and weight gain, visual changes, vertigo, tinnitus, bone damage, changes in kidney function, changes in heart rhythm.

Kaletra is not recommended for people with increased risk for heart disease as it can cause increases in lipids (blood fats) and high blood pressure. Your regular HIV monitoring will include tests to measure levels of blood fats (cholesterol and triglycerides).

Kaletra can cause pancreatitis. This nearly always occurs in people who have had it before, or who are on other medication that can cause pancreatitis.

Drugs not recommended for first-line HIV treatment

Some drugs are no longer recommended for standard HIV treatment in the UK. These include stavudine (Zerit), didanosine (Videx), saquinavir (Invirase), nevirapine (Viramune, Viramune prolonged-release), fosamprenavir (Telzir) and enfuvirtide (Fuzeon). This is because there are now more effective options, with fewer serious and long-term side-effects, such as peripheral neuropathy (damage to the nerves of the hands and/or feet) and fat loss or gain (lipodystrophy). There is more information on these later in this booklet.

Although these drugs are no longer recommended for people starting HIV treatment or changing to a new treatment, there may be people who are already on these drugs and happy to continue with them.

HIV treatment during pregnancy

If you have conceived when already on treatment, you can usually stay on your current combination of drugs, if these are successfully suppressing your viral load. If you are pregnant and have not yet started treatment, you should start on one of the combinations recommended in the BHIVA treatment guidelines for adults.

Many pregnant women have morning sickness – nausea (feeling sick) and vomiting (being sick) – in the first three months of pregnancy. If you are less than 12 weeks pregnant, and your CD4 count is high, you and your doctor could discuss waiting to start HIV treatment until morning sickness stops (usually at about 13 to 14 weeks). This is because some anti-HIV drugs can also make you feel sick during the first few weeks of treatment.

You should start HIV treatment by week 24 of your pregnancy at the latest. The combination used will depend on a range of factors.

Zidovudine (Retrovir) is not recommended for people starting treatment for their own health, but is still sometimes used as a short-term treatment to prevent mother-to-child transmission during pregnancy and birth. This is because there is good evidence that zidovudine is a safe and effective drug to use in preventing mother-to-child transmission.

Although zidovudine is the only drug licensed for use during pregnancy, it is now known that other drug combinations are effective in preventing mother-to-child transmission. So your treatment combination may or may not include zidovudine.

You can find out more about HIV treatment during pregnancy in the booklet in this series, HIV & women and you can get personalised information using our online tool HIV & pregnancy.

Zidovudine (Retrovir)

Very common and common side-effects: Nausea, vomiting, tiredness, headache, dizziness, stomach pain, muscle pain, feeling unwell, changes in blood counts, raised liver enzymes, fat loss.

Rare or uncommon side-effects: Rash, weakness, liver toxicity, lactic acidosis (high blood levels of lactic acid, a substance involved in metabolism).

Changing treatment because of side-effects

In some circumstances, you may need or want to change treatment because of side-effects. This is more likely to be an option if you have little or no resistance to anti-HIV drugs and your viral load is undetectable. Then you should be able to stop the drug that is causing your side-effect and switch to a different treatment.

Changing treatment can be more complex if you have a detectable viral load or you have HIV that is resistant to some anti-HIV drugs. Your doctor will look at the results of resistance tests and discuss possible treatment options with you. Having resistance will, however, limit the number of replacement drugs that are available to you.

It also makes good sense to ask about the possible side-effects of the drugs you are considering switching to.

Treatment for people who have taken a lot of anti-HIV drugs in the past

A number of anti-HIV drugs are now available that provide very important treatment options for people who have taken a lot of HIV treatment in the past, particularly those with drug-resistant virus.

These drugs are particularly effective against HIV because they work against the virus in a slightly different way to the older anti-HIV drugs, or work against virus resistant to other drugs in the same drug class. These drugs are:

  • maraviroc (Celsentri).
  • raltegravir (Isentress) and dolutegravir (Tivicay), also used by people starting treatment for the first time.
  • etravirine (Intelence).

Maraviroc (Celsentri)

Generally, people tolerate maraviroc well.

Very common and common side-effects: Nausea, diarrhoea, fatigue (tiredness), headache, depression, insomnia (difficulty sleeping), loss of appetite, stomach pain, rash, raised liver enzymes, weakness, anaemia.

Uncommon, rare and very rare side-effects: Liver problems, kidney problems, muscle inflammation, angina, cancers.

Rarely, maraviroc can cause a severe rash called Stevens Johnson syndrome, and very rarely serious liver toxicity. If you develop a rash with other symptoms, such as a fever, seek medical advice. See Hypersensitivity (allergic) reactions for more information and advice.

If you also have hepatitis B or hepatitis C, or have any other liver problems, your doctor should monitor you carefully and do blood tests to check the health of your liver.

Raltegravir (Isentress)

See Recommended first HIV treatment combination earlier in this section.

Etravirine (Intelence)

Generally, people tolerate etravirine well. It needs to be taken with food.

Very common or common side-effects: Rash, diarrhoea, headache, nausea, vomiting, reflux, stomach pain, anxiety, night sweats, insomnia (difficulty sleeping), fatigue (tiredness), raised lipids (cholesterol and triglycerides), diabetes, changes to blood counts, high blood pressure, peripheral neuropathy, kidney failure, heart attack.

Uncommon, rare and very rare side-effects: Liver problems, breathing problems, changes to heart rhythm, pancreatitis.

There is a risk of developing a hypersensitivity (allergic) reaction in the form of a severe rash (Stevens Johnson syndrome).

Side-effects

Published October 2017

Last reviewed October 2017

Next review October 2020

Contact NAM to find out more about the scientific research and information used to produce this booklet.

This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.
Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap
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This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.