Changing HIV treatment

There are a number of reasons why you may need to change your HIV treatment. If you are thinking about stopping or changing your treatment, talk to your doctor or another member of your healthcare team, so that they can support you to find the best treatment for you. It’s not a good idea to change treatment without first speaking to your doctor.

All drug regimens come with different pros and cons. Finding the treatment that is right for you is important. Your experience of treatment and adherence to it could be affected by many factors and it is important that they are managed in a way that works for you.

Due to advances in HIV treatment, there may be more options now than when the drugs you are currently on were chosen. Knowing what is available is key to ensuring that the treatment is sustainable for the long term and does not negatively impact on your quality of life.

Changing treatment because it isn’t working

Virological failure is when treatment fails to suppress the viral load effectively.

The aim of HIV treatment is to have a viral load that is ‘undetectable’, usually defined as below 50 copies/ml. Your viral load should fall to undetectable levels within six months of starting treatment. If it doesn’t, your doctor will investigate the reasons why and work with you to resolve this.

The most common reason for virological failure is missing doses and the development of drug resistance (see the next section for more on this.) It can also occur due to physiological factors, including suboptimal bodily absorption, distribution, metabolism, and excretion of the drugs (pharmacokinetics), having a very high viral load before treatment, and drug interactions.

Changing treatment because of resistance

Not taking your treatment as prescribed means that your viral load may increase to detectable levels. This means that the virus may become resistant to the anti-HIV drugs you are taking. Virological failure can occur because of this.

Before changing treatment, you should have blood tests to see which drug or drugs you have become resistant to. This is called ‘resistance testing’. These tests will help you and your doctor to choose the drugs that have the best chance of working against your HIV and be most effective for you. Resistance tests can only be done if your viral load is detectable.

When HIV develops resistance to one drug it can also develop ‘cross-resistance’ to other similar drugs as well.

A number of anti-HIV drugs are available as treatment options for people who have taken a lot of treatment in the past and who have drug-resistant HIV. It’s becoming easier to find a combination of drugs that is effective. The drugs in the combination will be chosen based on your individual resistance history and any intolerances you have to specific drugs.

• bictegravir (included in Biktarvy), an integrase inhibitor
• dolutegravir (Tivicay, also in Triumeq), an integrase inhibitor
• elvitegravir (included in Stribild and Genvoya), an integrase inhibitor
• darunavir (Prezista, also in Rezolsta and Symtuza), a protease inhibitor
• doravirine (Pifeltro, also in Delstrigo), a non-nucleoside reverse transcriptase inhibitor (NNRTI)
• etravirine (Intelence), an NNRTI
• fostemsavir (Rukobia), an attachment inhibitor 
• ibalizumab (Trogarzo), a post-attachment inhibitor
• maraviroc (Celsentri), a CCR5 inhibitor
• lenacapavir (Sunlenca), a capsid inhibitor.

Other treatment options are in development for people with drug-resistant HIV who are highly treatment-experienced, some of which work against HIV in completely new ways.

You can find out more on our page Resistance to anti-HIV drugs.

Changing treatment because of side effects

All drugs can cause side effects and the drugs used in treating HIV are no exception. The most common side effects happen soon after you start treatment with a drug, but some only develop when you’ve been taking a drug for months or even years.

Sometimes you may experience a symptom and not be sure whether it's a side effect of a drug or a symptom of something else. Talk to your doctor, or another member of your healthcare team, about any concerns you have. You shouldn't feel that you have to cope with side effects alone.

It is particularly important to talk to your doctor if you develop a rash (even one that isn’t severe) or fever soon after taking certain drugs, such as abacavir (Ziagen, also in Triumeq), nevirapine (Viramune) and etravirine (Intelence), as this could be a sign of an allergic reaction. Other side effects can get worse the longer you leave them, so it’s best to mention them as soon as they develop.

If side effects cause problems, changing treatment may be an option.

As all anti-HIV drugs can cause side effects, it is possible that the drug you switch to might have other side effects. There is also a chance that you might find your new treatment harder to take or that it is not as effective as your previous treatment. If this happens, your doctor should be able to find a more suitable combination, or switch you back to the medication you were on before.

Longer-term side effects will be carefully monitored by your doctor as some may only be apparent with laboratory tests. If you are concerned about anything listed below, please speak to your doctor and they can discuss your concerns.

Some of the more common potential long-term side effects of specific drugs are:

• Central nervous system adverse events (such as impaired concentration, mood swings or sleep disturbance) – efavirenz (Sustiva) and dolutegravir (Tivicay, also in Triumeq, Juluca and Dovato).
• Kidney problems – tenofovir disoproxil (Viread, also in Stribild and Eviplera) and protease inhibitors boosted with ritonavir or cobicistat.
• Liver problems – nevirapine (Viramune).
• Low bone mineral density – tenofovir disoproxil (Viread, also in Stribild and Eviplera) and protease inhibitors boosted with ritonavir or cobicistat.
• Weight increase – integrase inhibitors and tenofovir alafenamide (included in Descovy, Odefsey, Genvoya, Symtuza and Biktarvy).
• Lipid abnormalities (raised cholesterol or triglyceride) – efavirenz (Sustiva) and lopinavir/ritonavir (Kaletra).

If you already have one of these health issues, it would be best to avoid a drug that might make it worse. Your doctor will discuss any changes in your health with you. This will help to determine if and when you need to change treatment.

Although the above drugs are associated with those side effects, other HIV and non-HIV-drugs can also cause similar side effects. Therefore, the evaluation of cause and effect has to be done carefully by your doctor using your medical history.

You can find out more on our page Side-effects of HIV treatment.

Changing treatment because of drug interactions

Many people living with HIV need to take treatment for other health conditions. Taking two or more different drugs together could alter the effectiveness or side effects of these drugs.

When you are being prescribed or dispensed other drugs, it is important that the doctor or pharmacist is aware of which antiretrovirals you are taking. This includes any over-the-counter medicines, vitamins, herbal and alternative drugs and recreational drugs. Avoiding possible drug interactions is key to ensuring that the treatment works effectively.

Some drug combinations are contraindicated – which means you definitely should not take them together. If taken together, it could cause serious side effects, or interactions which make one or both drugs ineffective or toxic. Other possible interactions are less dangerous, but still need to be taken seriously. Levels of one or both drugs in your blood may be affected and you may need to change the doses you take.

Your HIV doctor and pharmacist will monitor possible interactions before prescribing new medicines to you. They may suggest changing your anti-HIV medication to avoid interactions. The University of Liverpool has a helpful resource for you to be able to easily check what drug-drug interactions may occur.

You can find out more on our page on HIV treatment and drug-drug interactions.

Changing to a simpler treatment

You might be able to change your treatment to one that involves fewer pills, fewer doses or fewer constraints, making it easier to take. There may be more treatment options available to you now than when you started your current regimen, due to advances in HIV treatment. Simplification could involve switching from a triple-drug regimen to a two-drug regimen.

Complicated treatment regimens are a common problem, particularly if you are taking medication for other health problems too. It is important that your doctor works with you to try and alleviate this.

Food requirements can be a barrier to a good quality of life and adherence. For example rilpivirine (Edurant) must be taken with a full meal, whilst efavirenz (Sustiva) must be taken on an empty stomach. These requirements won’t work for everyone. You might be able to change to drugs without food restrictions.

As some drugs raise the risk of some long-term health problems, regular monitoring of cholesterol, bone problems, liver function or kidney function may be required. Monitoring needs vary for each regimen; changing treatment could also reduce the number of tests you need to have done.

Changing treatment because of pregnancy

If you are planning a pregnancy or have recently become pregnant, you may need to switch to a different treatment. It is worthwhile speaking to your doctor if you are planning a pregnancy sooner rather than later. If your viral load is not undetectable, you may need to change treatment to achieve a rapid viral load decline.

If you are on any of the following treatments, your regimen may have to be modified:

• darunavir/cobicistat (Rezolsta, also in Symtuza)
• elvitegravir/cobicistat (included in Stribild and Genvoya).

If you are taking raltegravir (Isentress) once a day, you may need to switch to taking it twice a day.

Changing treatment because of hepatitis B

If you also have hepatitis B, you may need to change your treatment to include either tenofovir disoproxil or tenofovir alafenamide, as these also treat hepatitis B. You can switch from one of these drugs to the other, but once you have started to take tenofovir, it is important not to stop it, as this can cause hepatitis B flare-ups and increase the risk of liver problems.

Changing treatment because of cost

Your doctor may suggest switching to a different drug that is as effective, but is less expensive.

Or they may ask you to switch to a generic drug. This is a medication created to be the same as an existing approved brand-name drug. Generic drugs are the same in performance, safety, strength and quality. As more of these become available, you may switch to them to reduce the cost of your medication.

You can find out more on our page Which HIV medications are available as generics?

Staying on the same treatment for a long time

In some cases when the treatment is well-tolerated and effectively suppresses the virus, your doctor may not recommend newer alternatives or you may opt to stay on the regimen despite knowing about the existence of potentially simpler or safer regimens. The idea may be 'if it’s not broken, don’t fix it'.

As long as your current treatment does not lead to potentially harmful long-term health effects, it might still be a good option. But in some cases your doctor may simply be too busy to pay attention and/or you may be unaware of better alternatives.

This is why it is important for people with HIV to stay informed and advocate for their own health. Instead of waiting for your doctor to recommend a change, you can be proactive and talk to your doctor about potential improvements to your treatment regimen. 

Things to consider when changing treatment

It’s up to your doctor to evaluate your situation and recommend appropriate new treatment that will address the problems you have with your current treatment. This is why it is important to openly discuss any issues and concerns you have so that they can suggest the right treatments. In some cases, your doctor may propose a few options and you can use the following considerations to weigh the pros and cons of each option.

Could the new regimen make current side effects worse?

For example, if you are switching from a drug such as dolutegravir because of neuropsychiatric side effects, choosing efavirenz (also known for similar effects) would not be the best option.

Could the new regimen cause negative long-term health effects such as kidney or liver damage?

For example, if you are offered tenofovir disoproxil, you need to consider the slim but real possibility of kidney damage in the long term.

Does the new regimen have a high barrier to resistance?

Some drugs and drug combinations are very difficult to develop resistance against; generally the higher the barrier the better. Integrase inhibitors such as dolutegravir and bictegravir have a high resistance barrier.

Is the new regimen taken as a single tablet, multiple tablets or via injections?

The pros and cons of single- and multiple-tablet regimens are a matter of individual preference. Injectables offer relief from daily pills, but require regular medical visits. The frequency depends on the regimen:

• cabotegravir with rilpivirine (Vocabria plus Rekambys) once a month
• cabotegravir with rilpivirine (Vocabria plus Rekambys) once every two months
• lenacapavir (Sunlenca) once every six months.

Currently there are attempts to formulate other common HIV drugs as injectables too, therefore there may be more options in the near future.

Could the new regimen limit your future treatment options in case of potential resistance?

Some drugs and combinations of drugs can lead to what is known as cross-resistance. This is when resistance to one drug leads to resistance to several other similar drugs, which can eliminate a few future treatment options at once. For example, resistance to rilpivirine can lead to varying levels of resistance to other drugs in the same class (non-nucleoside reverse transcriptase inhibitors; NNRTIs).

Is the new regimen forgiving?

A forgiving regimen maintains sufficiently high levels of the drugs in your blood for a longer period; this may prevent the development of resistance even when you miss a dose. Because you may unintentionally miss a dose on some occasions, a more forgiving regimen is generally better.

Does it have many drug interactions?

Some drugs such as boosted protease inhibitors (like atazanavir and darunavir) have more drug interactions, while nucleoside reverse transcription inhibitors (NRTIs – like lamivudine, abacavir and tenofovir) have almost no known interactions. Integrase inhibitors (like bictegravir, dolutegravir and cabotegravir) have very few significant interactions and these are easily avoidable. NNRTIs (like rilpivirine, doravirine and efavirenz) have a few interactions that are generally easy to prevent.

You can use the University of Liverpool’s resource to check for individual drug interactions. 

Does it have interactions with any supplements?

You may be taking supplements to optimise your general health or exercise performance. However, some supplements may impact on your HIV medication. Generally, NRTIs have nearly no supplement interactions, but integrase inhibitors cannot be taken with divalent cation mineral supplements such as magnesium, calcium and iron, unless taken with a meal. Garlic and gingko biloba supplements may lower the concentration of some protease inhibitors. 

You can use the University of Liverpool’s resource to check for individual drug interactions. 

Does it have any food requirements?

For example, rilpivirine in pill form requires a full meal. Generally, food intake has no effect on NRTIs, and newer generation integrase inhibitors (dolutegravir and bictegravir) have no meal requirements either. Most protease inhibitors are recommended to be taken with food.

You can find out more on our page Food requirements for anti-HIV medications.