Combination therapy means taking a combination of HIV treatments otherwise called antiretroviral drugs. There are five types or classes of these drugs, each of which work in different ways against HIV.

This chart lists currently available drugs in Australia and their doses.

It is now known that the most effective way to treat HIV is by combining different classes of drugs that attack the virus in different ways.

A number of companies have co-formulated some of their drugs into one pill. So sometimes you may be on one or two different pills but three different drugs.

It is standard practice to commence and maintain people on a combination of at least three drugs from at least two of the five following classes.

The five classes of drugs are:

• nucleoside and nucleotide reverse transcriptase inhibitors (or ‘nukes’ or NRTI/NtRTI)
• non-nucleoside reverse transcriptase inhibitors (‘non-nukes’ or NNRTIs)
• protease inhibitors (or PIs)
• integrase inhibitors
• entry inhibitors

The most common combinations include two nucleoside reverse transcriptase inhibitors, in combination with a non-nucleoside reverse transcriptase inhibitor, protease inhibitor, or integrase inhibitor.

Every time HIV reproduces itself there’s a chance that it may ‘mutate’ slightly. These mutations may make the virus more resistant to an individual drug or potentially a class of drugs. The more the virus is reproducing (i.e. the higher the viral load) the more chances of mutations occurring.

Three drug combinations are most frequently used because they stop most virus reproduction, and because the chances of a mutation becoming resistant to a number of drugs at the same time are small.

If you miss doses regularly or stop taking the drugs for a few days, you give the virus a chance to mutate. And because small concentrations of one or more of the drugs you are on can still remain in your bloodstream, any mutations which are resistant to these drugs will multiply better and have more chance of infecting new cells. So, each missed dose can mean slowly rising levels of resistant virus in your body. Missing doses regularly may allow the virus to escape the control of a drug.

If the virus does develop resistance, the treatments become much less effective and your choices of available drugs to use in the future may be limited. If this happens, HIV can keep multiplying in spite of the drugs, effectively behaving as untreated virus. This is why increases in viral load can mean you need to change treatments.

A few tips to help stop the development of resistance

• Take the full dose of each drug as prescribed. This allows the drug always to be working at maximum capacity.
• If you miss a dose, don’t double up on your next dose. You just risk more side-effects but won’t have a better result against the virus.
• Take all the drugs in your combination regularly. This means the drugs are always in your blood at levels that work effectively against the virus.
• If you are having difficulties taking a certain drug because of side-effects or dose requirements, talk to your doctor about changing to a combination that suits you better and is easier to remember. It is better to change treatments than to stay on a combination which doesn’t suit.

Treatment is now recommended for all people with HIV, regardless of disease stage so the question of ‘when to start’ primarily depends on your readiness and may include a wish to reduce your infectiousness.

For people with early HIV infection

If you currently have or recently had a seroconversion illness (within the last 6 months) some scientists and doctors believe that starting treatment at this point may have benefits in preserving the health of the immune system over the long term. The symptoms of seroconversion, which are similar to ‘flu, and are sometimes severe, may be alleviated by starting treatment immediately.

There is also evidence that men with recent HIV infection have higher levels of HIV in their semen, thereby increasing the likelihood of sexual transmission of HIV. By starting treatment in the first few weeks of HIV infection, this could help reduce the risk of transmission to sexual partners.

For people with chronic HIV infection who remain “well”

Previous treatment guidelines and the associated funding allowed HIV treatments to be prescribed if the CD4 count was below 500, the viral load about 10,000 copies/ml or if the patient had symptoms or signs of HIV illness.   Current treatment guidelines allow treatment at any stage of HIV infection, including for CD4 counts >500 and recommend that treatment be offered regardless of CD4 cell count.

This shift to recommending treatment for all people with HIV comes as a result of findings from a large clinical trial in 2015 that found a benefit of treatment for people even with high CD4 counts.

The viral load is less important in determining when to start medication, but if the viral load is greater than 100,000 copies per ml, this might be another factor in starting treatment earlier rather than later. The goal of treatment is to prevent progression of HIV disease and the development of symptoms of HIV disease.

A wish to reduce infectiousness is also a valid reason to commence treatment at any disease stage.

For people with a history of an AIDS defining illness, a CD4 count below 350 or severe symptoms of HIV disease regardless of CD4 count

Treatment is recommended for any person with symptoms of HIV disease including neurological HIV disease or a current or past opportunistic infection. The goal of treatment is both improvement in health and the prevention of further damage to the immune system or reoccurrence of opportunistic infections.

 

Treatment readiness

Starting antiretroviral therapy is a serious commitment because it means taking treatments for the rest of your life (treatment breaks are no longer recommended). However, there is now evidence that commencing ARV treatment upon diagnosis yields immediate, lasting benefits and is the best thing you can do for your health.

Modern treatments are much better tolerated than they used to be. While side-effects may still affect your quality of life, this is not common and for many people side effects are minimal or non-existent. Many side effects occur in the first few weeks but then pass as your body gets used to the drugs. Many people experience improvements in health and energy levels after starting antiviral therapy. Similarly, treatment regimes are no longer as burdensome as they once were. Several ARV treatment options consist of a single tablet per day.

If you aren’t ready to start combination therapy, it’s important to think about how you will become ready in future. Any treatment decision needs to be discussed fully with your doctor taking into account viral load, CD4 and how you plan to  integrate combination therapy into the way you live.

What combinations are best?

There are lots of possible combinations of HIV drugs. It’s not possible to describe them all here. Further, people will respond differently to the same combinations, for a variety of reasons.

Some drugs can’t be used in combination for clinical reasons (e.g. they compete with each other to get absorbed into the body), or other reasons (e.g. they have the same side-effect). Work with your doctor to choose the best drugs, considering some of the factors listed below:

• What stage of disease are you at (viral load, CD4 counts, symptoms)?
• What prior treatment, if any, have you had?
• Do you have other health conditions and/or take other medications?
• How easy will it be to take the particular combination?
• What are the possible side-effects?
• If the tablets must be taken with food, consider whether your eating habits are amenable (e.g. do you skip meals regularly?).
• Are there confidentiality issues around taking tablets in some contexts?

Australian HIV treatment guidelines  reference international guidelines and are updated regularly. These may contain recommendations about which drugs or combination of drugs to take in particular circumstances based on the latest evidence.

Adherence (also called compliance) means the extent to which you take the right dose of the drugs at the right time. Skipping doses can mean that the drug becomes less effective against the virus and allows resistance to develop. Taking a drug on a full stomach when it’s meant to be taken on an empty stomach can make it less effective because it is less well absorbed and the level in the blood stream will be lower. Make sure you know how each drug should be taken to ensure it is as effective as possible.

Are you having trouble with your dosing schedule?

There are many ways to remember to take your drugs on time. You could experiment with some of these:

• Take your drugs at the same time each day.
• Have supplies of your drugs at places you know you’ll be (partner’s house; work).
• Keep a backup dose in a portable pill container in your bag in case you forget to take a dose at home, but be aware that medications expire so swap over your spares from time to time.
• When travelling, plan to adjust your schedule for different time zones you might be going to.
• Use your phone or calendar to set an alarm or reminder notice.
• Get a dosette box — this is a box which lets you set out your pills for the week in labelled sections so you can easily see what you have taken and what you need to take next. These are available from chemists. Camping supply shops also sell small plastic jars that can be useful for storing backup doses.
• Use a calendar or diary in a prominent place at home and work which you can tick off each time you take your pills.
• Establish a routine which associates pill taking with meals where appropriate.
• Prepare for travel or holidays by getting a stock of drugs in advance — always take extra in case you experience travel delays. If flying, always pack your medicine in your carry-on hand luggage — if the airline loses your checked bag you still have your drugs. Here are some tips about travelling with HIV drugs.
• Get tips from other people with HIV about how they remember their pills.
• The National Prescribing Service not only has a handy ‘phone app in which you can record the names of you medication(s), it will also answer questions (by email) about drug interactions, should you be prescribed something by a doctor to whom you have not disclosed your status or that you are on HIV medication.

You may need to change your treatments for a number of reasons. If there are sudden unexplained changes to your viral load, it could mean that the virus has become resistant to one or more of the drugs in your combination.

You may also need to change combinations if you are unable to meet the requirements for dosing schedules, or if you are finding the side-effects intolerable, even if your viral load and CD4 levels are OK.

If you have severe side-effects due to a particular drug or class of drugs there may be other combinations that can be recommended. It is important that you speak with your doctor before stopping any of your HIV antiviral treatments.

You will need to be monitored after each change in combination to see how the new one is working. During these times, you will probably need more frequent viral load tests.

Treatment breaks

In the past, when side-effects were more severe, some people would take treatment breaks or ‘structured treatment interruptions’. This is no longer recommended as people who do this are at higher risk of developing opportunistic infections and have a higher risk of cardiovascular disease (mostly heart attacks and strokes) and reduced life expectancy in the long term.

Sometimes, people stop treatments for just one or two days, either deliberately such as during a party weekend or accidentally because they forget. Modern treatments are more forgiving than their predecessors; however, such breaks should be avoided if possible, as they present a risk of developing resistance.  Many of the medications in the newer combination single tablet regimins have different half lives, meaning that some medications take longer to leave the blood stream than others.  A low level of a medication and a rapidly reproducing virus means that more mutations resitant to the medication may be able to flourish.

Nevertheless, some people do feel the need to take longer, planned breaks from HIV drugs. This may be because of side-effects, the desire to ‘have a rest’, or other factors, like overseas travel. You should discuss this thoroughly with your doctor. Factors like viral load and CD4 counts are very important. If you have a very low CD4 count, stopping treatments could put you at risk of developing an opportunistic illness. You should consider whether you need prophylactic treatment during this time.

If you do want to stop your drugs for whatever reason, it is important to discuss this with your doctor and develop a plan. If a person is having major life difficulties that disrupt adherence, it may be more sensible to stop all the drugs and work through these problems before trying again.

Any drug can cause side-effects, or unwanted effects. These can be divided into different types:

• allergic reactions
• initiation side effects (when you start the drug) which will settle with time
• ongoing side-effects
• long-term toxicities or effects which can develop over a number of years

Not everyone gets side-effects from their drugs and not everyone experiences the same side-effects: many are quite rare.

It’s hard to estimate how often people develop different side-effects; however diarrhoea, headaches, nausea and gastrointestinal upset to some degree are not uncommon with many HIV treatments. In the vast majority of cases these side-effects are manageable and often decrease after the first month or so.

Allergic side-effects or ‘adverse reactions’ to a drug are unpredictable — a few people may suffer them, but the majority won’t. Adverse reactions can occur when the immune system reacts badly to a drug and the symptoms are usually a rash or fever. Often, these symptoms will resolve themselves, but if you develop a rash when beginning a drug, seek medical advice as on rare occasions some allergic reactions can be dangerous. You may be able to treat the rash with antihistamines, or by slowly increasing your dose as your body gets used to the drug.

However, wherever a drug has been shown to potentially cause adverse reactions, it will be accompanied by a warning in the product information sheet or packaging included with the drug. Your doctor will also advise you about it, and what to do if something like a hypersensitivity rash occurs when taking abacavir.

Direct reactions to the drugs can cause a range of, sometimes, ongoing side-effects which can vary from mild (headache or occasional diarrhoea) to more serious. There are also some problems which may develop over time, like numbing of the fingers and toes, abnormalities in liver function, or abnormal redistribution of fat throughout your body. These are powerful drugs and therefore some side effects are to be expected.  However most people are side effect free.

Your doctor may prescribe other medicines (like anti-diarrhoea or nausea medications) to help deal with some of these. Many people report that some complementary therapies or dietary changes are useful in controlling side-effects; talking to an HIV-experienced dietician may be beneficial. Referrals will be available through your doctor.

Some side-effects to HIV drugs can develop over the long-term. Now that we know more about these drugs, doctors are increasingly monitoring and checking for signs of these problems, and may advise you to change drugs if you are at risk. These include:

• peripheral neuropathy, or nerve damage causing pain in hands or feet
• blood sugar changes
• high cholesterol or blood fats
• body shape changes like fat wasting or developing a belly, paunch or enlarged breasts (lipodystrophy)
• muscle inflammation
• anaemia
• hepatitis and pancreatitis (inflammation of the liver or pancreas)
• mouth ulcers.
• some effect on mood, though this can be hard to tease out from other things going on in life

The earlier you detect any side effects, the easier it is to make changes to diet, exercise or the medications themselves, which can all help improve, or in some cases reverse these effects.

Some people who have taken a wide range of antiviral drugs over many years, may have virus which is resistant to some classes of drugs. Treatment of multi-drug resistant HIV has sometimes been referred to as ‘salvage therapy’. This may include:

• using newer drugs that are active against resistant strains of HIV
• recycling drugs — that is, using drugs you have previously used in conjunction with resistance testing to determine which ones may work best
• ‘mega-HAART’ regimens — using combinations of more than three antiviral drugs. These regimens, of course, may pose side-effect problems
• ‘treatment intensification’ — adding one or two drugs to an existing regimen.

Most people with multi-drug resistant virus can be offered effective alternatives these days

At some times, you may need to take other medicines, like antibiotics, for specific infections or symptoms. It is important to find out from your GP, pharmacist or specialist whether these are likely to interact with the HIV treatments you are on.

Some complementary medicines can interact negatively with HIV treatments. It is important to let your doctor know if you are taking any herbs, vitamins, traditional Chinese medicines or other complementary medicines.

The National Prescribing Service website is staffed by specialist pharmacists who will answer email queries about side effects, drug interactions, and evidence

There’s not a lot known about the interaction between HIV treatments and illicit or recreational drugs, though this is changing. However, if you do take recreational drugs, there are some harm reduction measures you should consider.

• Avoid taking HIV drugs and other drugs at exactly the same time: wait at least a couple of hours between doses.
• Ritonavir and possibly other protease inhibitors may cause dangerous, even fatal interactions with ecstasy, crystal/ice and other types of methamphetamines.
• Drink plenty of water.
• Start with a smaller amount of any illicit drug and monitor any unusual responses.
• Seek emergency medical help if you experience dizziness, sudden drowsiness, blurred vision, heart palpitations, vomiting or any other severe or unexpected effect.
• Methamphetamines and ecstasy can often cause loss of appetite and even make eating difficult, which can be a problem for people who need to take treatments with food.

As our understanding of HIV tests and treatments continues to expand, it can be useful to stay abreast of developments. A good way to keep up to date is by reading regular treatments publications like Positive Living. Positive Living is produced by the National Association of People with HIV Australia (NAPWHA) and is available from the NAPWHA website.

The Institute of Many is an online forum for people with HIV. Discussions about treatments are common and it is possible to share experiences with other members on many aspects of HIV treatments.

Some AIDS Council’s and HIV positive organisations also publish newsletters containing regular treatment news.

The following websites may also be useful:

• The Body (US): www.thebody.com
• AIDSmap: www.aidsmap.com
• Canadian AIDS Treatment Information Exchange: www.catie.ca
• Project Inform: www.projectinform.org