Do the drugs really work?

In every country that uses combination therapy (three or more drugs to treat HIV - also called HAART (Highly Active Anti-Retroviral Therapy) AIDS-related deaths and illnesses have dropped dramatically.

Treatment works for women, men and children. It works no matter how you were infected with HIV. Whether this was sexually, through IV drug use, or by blood transfusion.

Taking HIV drugs, exactly as prescribed, will reduce the virus in your body to tiny amounts. This then lets your immune system recover and get stronger by itself.

Regular monitoring, using blood tests, will check that the drugs continue to work

Even if you start with a very low CD4 count, you could regain enough of your own immune system for your body to recover from many HIV-related illnesses.

If you use HIV treatment at the right time, and in the right way, you should stay well much longer.

How long will the drugs work?

Combination therapy using at least three drugs has now been used for over six years. Many of the individual drugs have been studied for even longer.

The length of time that any combination will work depends mainly on you not developing resistance. This depends on getting, and keeping, your viral load to undetectable levels, below 50 copies/ml.

If your viral load stays undetectable, you can use the same combination for many years.

UK guidelines state that getting your viral load below 50 is a main goal when starting treatment.

Does everyone need treatment?

At some point, most HIV-positive people will need treatment. When people will need it though, can vary a lot. HIV infection progresses in different people at very different rates.

Whether you need treatment is something you have to discuss with your doctor. This will usually take place over several visits.

When discussing treatment:

Even if you are well, it is a good idea to get to know something about treatment now, before you need it.

This is particularly important if your CD4 count is falling, or if you have a high viral load.

When should I start treatment?

When to start treatment is something you and your doctor must discuss together. You are the person who has to take the pills. So you have the choice over whether you start, as well as which drugs you use.

It is recommended to start treatment before your CD4 count falls below 200. Even at this level, there is unlikely to be an urgent need for you to start treatment straight away, if you are not ready.

While your CD4 count is above 300 you still have a good immune system. Below 300 you are at a higher risk of infections that cause diarrhoea and weight loss.

If your CD4 count falls below 200, your risk of developing a pneumonia called PCP increases. If it falls below 100, then your risk of serious illnesses increases even further.

A low CD4 count does not mean that you will definitely become ill. It is, however, much more likely. Most of the drugs used to treat these HIV-related illnesses can be more toxic and difficult to take than regular anti-HIV drugs.

Although you may be worried about using treatments, HIV and AIDS is still a very real and life-threatening illness. It is possible to delay treatment until it is too late. Illnesses that can occur at any time when your CD4 count is below 200 can be fatal.

Are recommendations the same for men and women?

There are some differences between HIV in women and men. One of these is that at the same CD4 count, women can have a slightly lower viral load than men. Some studies also show that women have a higher risk of becoming ill than men at the same CD4 count. This may be a reason for women to start treatment earlier than men. The evidence to support this was not strong enough for this to be included in treatment guidelines.

An American study found that viral load levels vary during the different stages of the menstrual cycle. It may be a good idea, for you and your doctor, to make a note of where you are in your cycle when you have these tests. You can then make an allowance for this when you get the results.

What about treatment in pregnancy?

Studies have shown that women’s HIV can be effectively treated during pregnancy.

How do children use HIV treatment?

The principles for treating children with HIV are very similar to those for treating adults. But, there are some important differences.

The immune system and drug absorption can be different in babies, toddlers, infants, children, adolescents and adults. This is why specialist HIV care is recommended at all ages.

For this reason, there are separate treatment guidelines for treating children. However, they tend to be updated less frequently than adult guidelines. It is therefore important to be aware of changes in adult care that may be just as relevant for children.

Adherence is the term for taking all your medications exactly as prescribed. This is also essential at any age. Resistance can develop regardless of age if you use a treatment that does not get your viral load to undetectable levels.

Is age an important factor in adults?

Combination therapy may reactivate an important part of your immune system called the thymus. Previously, most doctors thought it stopped working in adolescence.

One study showed that the thymus may become active again in people in their 30s who are HIV-positive and using combination therapy. This finding isn’t yet fully understood. It may mean that there are advantages to starting treatment when in your 20s or 30s in order to make use of this.

Ageing itself suppresses our immune systems. People over 50 have an increased risk of damage caused by HIV. The argument for starting treatment becomes stronger as you get older.

Treatment guidelines do not yet comment on this apart from in reference to heart disease (see below).

Age, HIV drugs and heart disease

Risk factors for heart disease include age (over 45 for men and over 55 for women), sex (male), lack of exercise, family history of heart disease, high blood pressure, smoking and diabetes.

Other risk factors associated with heart disease include raised levels of cholesterol and triglycerides, which can be a side effect of HIV treatment.

Although the benefits of HIV treatment far outweigh the additional risks of heart disease for most people, this may not be true for everyone. The additional risks that HIV treatment may generate, means that an assessment of cardiovascular and HIV risk factors should be made before starting HIV treatment.

Take, for example, a 55-year-old male smoker who is otherwise well, but takes little exercise. He may be better to delay treatment until he makes lifestyle changes that reduce some of these cardiovascular risks. If his HIV risk factors are also high (if he has a low CD4 count or a high viral load), then lifestyle changes become even more important.

Early diagnosis and primary infection

Some people who discover that they are HIV-positive within six months of being infected decide to start treatment straight away. This is regardless of their CD4 and viral load counts.

People treated in this six-month period hold on to a part of their immune system that is ordinarily lost in almost everyone without treatment. It is retained, however, by people in whom HIV progresses only very slowly. This is the HIV-specific immune response.

Unfortunately, researchers have not yet been able to turn this interesting finding into an improved health benefit. Using early treatment may enable you to benefit from immune treatments or vaccine-related research in the future.

But, you need to balance these potential benefits against side effects and the risk of resistance. Also, that you may not medically need treatment for many years. Treatment in primary infection is therefore largely only provided in clinical trials.

Late HIV diagnosis and low CD4s

Some people, across all age ranges, only find out they are HIV-positive when they become ill and admitted to hospital. This often means starting treatment straight away, especially when the CD4 count is below 100 cells/mm3.

For people who only discovered they are HIV-positive when their CD4 count is very low, there is still very good news.

Even with a very low CD4 count, even below 10, if you follow your treatment very carefully, you can expect treatment to work. Your viral load will drop and your CD4 count will rise again to safer levels.

What about side effects?

Everyone considering HIV treatment worries about side effects. But most people find that, within a few weeks, taking treatment becomes an ordinary and manageable part of their daily life.

Ask your doctor, nurse or HIV pharmacist about the most common side effects of the drugs that you want to use. Ask how likely they are to occur. Ask how many people stop treatment because of them (usually very few). Even rough estimates will give you a good idea of what is involved.

Nausea, diarrhoea and tiredness are the most common general side effects. These often become easier after the first few weeks. Very rarely, nausea and tiredness can be very serious. This is why you should tell your doctor of any problems.

Ask your doctor or pharmacist for anti-nausea and diarrhoea medications when you first start therapy so you can use these as you need them.

If these medications aren’t effective, ask your clinic for stronger or more effective drugs.

Lipodystrophy

Lipodystrophy refers to changes in blood fat and blood sugar levels. It also includes changes in fat cells and the distribution of body fat.

It is a set of side effects that is a worry for many people who are about to start treatment.

However, most severe cases of lipodystrophy are in people who have used many different drugs, or have used treatment for many years. The greater awareness of lipodystrophy today means that you will be monitored carefully. You can change treatment if you get low-level symptoms. More importantly, new drugs to use in first-line therapy, which are less likely to cause these side effects, will hopefully reduce the incidence of lipodystrophy.

Different drugs may be responsible for fat gain and fat loss. Fat accumulation, to the stomach or breasts and/or across the shoulders, has been more linked to protease inhibitors and NNRTIs. Fat loss, from arms, legs, face and buttocks, has been linked to nucleosides. This is mainly to d4T, and to a lesser extent to AZT.

We do not know what causes lipodystrophy. Symptoms can occur rarely in HIV-positive people who are not on treatment. Lipodystrophy usually, but not always, develops slowly over many months.

Early symptoms may reverse if you switch to different HIV drugs. Exercise and dietary changes can also help.

Careful body measurements by a dietician, by DEXA scan, or photographs can monitor changes.

Regular blood tests will check for other side effects. If you have any difficulties make sure your doctor takes them seriously and does something about it.

Other side effects

Side effects that are more serious occur rarely with most combinations. They also relate to specific drugs. It is important to be aware of those associated with the drugs that you will use before you start treatment.

See Managing Side Fx

What is the best combination?

There isn’t an answer to this question. This is because drugs that agree with one person can be impossible to tolerate for another. See Starting Combinations

Any combination should cover two things:

Your doctor will discuss with you which combinations are more likely to get your viral load undetectable. If you have taken HIV drugs before, this will affect how well your next treatment works.

Ask for information about dosing schedules, pill size and side effects. This will help you pick a regimen that will be easier to follow.

Can I change treatments?

If your first combination is too difficult to follow, or if any initial side effects have not improved after the first few weeks, you can always change the drug or drugs that you find most difficult.

If this is your first combination, you have many choices. You should not put up with difficult side effects for months on end.

Many people use one combination to get their viral load undetectable, and then change to an easier combination afterwards.

Can I take a break in my treatment?

Treatment breaks have received a lot of attention. Originally, and not very helpfully, they were called ‘drug holidays’. Other names include STIs, which stands for Structured (or Strategic) Treatment Interruptions.

Stopping treatment may help people who are resistant to the available drugs. This is when you may have no other treatment options. In this situation a treatment break should be for a short period - perhaps only for two months. One recent study showed that a break of four months was worse than not taking a break.

Another reason to use STIs may be to manage long-term treatment. Several trials are looking at stopping and restarting treatment based on their CD4 count. This is only recommended as part of a trial.

Other trials looking at how the immune system responds to HIV did not find a benefit from planned treatment interruptions.

What does ‘treatment naive’ mean?

The term for someone who has never used any anti-HIV drugs before is ‘treatment-naive’ or ‘drug-naive’. This is a very special position to be in. It means that any of the available drugs should work.

The first time you use anti-HIV drugs is the time they are most potent. This is why it is best to get it right first time.

Should I enter a trial?

Many hospitals are also research centres and you may be asked to join a trial.

Remember, many combinations are already available to use that have proven their effectiveness. There is no need to join a trial if you do not want to.

Treatment is now recommended when your CD4 count is about 200 cells/mm3. This should also be the case for new HIV treatment in trials. If your CD4 count is much higher than 200, then it should be clearly explained to you that treatment would not be routinely recommended.

Well planned studies can offer better monitoring and care than you would normally receive at your regular clinic. This may mean attending your clinic more frequently.

If asked to join a trial, or if you are interested in a trial, take plenty of time to find out about it. Ask for independent advice. Women should ask the percentage of women that are included in the study.

Trials are very important for developing new treatments. They can improve our knowledge of how to use both new and existing drugs. However, if you are recently diagnosed, or are only just finding out about treatment, you should not feel pressurised into taking part.

Ask about the alternatives to the treatment proposed in the study. Ask what advantages the study offers over existing treatment.

Your future care will not be affected if you choose not to take part in a trial.

What else do I need to know?

Ongoing research means that ideas about how to use anti-HIV drugs are changing. The treatment your doctor will advise today is likely to be different from 12 months ago.

This isn’t just because there are newer drugs available. It is to do with understanding how the drugs work, why they sometimes stop working, and especially increasing knowledge about resistance.

Ask questions about anything you don’t understand. You can then take responsibility for whatever you decide.

Why do treatments not always work?

For some people the treatments will not work as well. There are several reasons why:

Trial results never show a 100% success rate. BUT if you have a good doctor, and you follow your regimen carefully, anyone starting treatment for the first time should be able to get an undetectable viral load.

Success rates for people on their second or third therapy are usually lower than for those starting treatments for the first time.

This is often because people continue to make the same mistakes and move to a new combination without understanding why the original one failed.

This booklet concentrates mainly on the effect of treatment on viral load and CD4 results. This is because these are the main markers that doctors use to decide if a treatment is working. Some people may never reach undetectable levels but still stay well and healthy for many years. There are always more responses to treatment than can be summarised here.

You may not get an undetectable viral load, perhaps because of resistance.

However, you can still benefit from continuing treatment. You could also benefit from new drugs developed in the future. New drugs are available before full approval through early-access programmes.

If you need new drugs in order to put together a new combination then make sure you and your doctor keep up-to-date on the latest research.

For more information on second-line and salvage treatment, see the i-Base ‘Guide to Changing Treatment’.

Are the drugs a cure?

The current drugs are a treatment but not a cure. They stop the progression of HIV. They let your immune system start to repair itself. But, you will still be HIV-positive.

Even people taking combination therapy for many years, with a viral load below 50 copies/ml, still have very small amounts of HIV. This HIV is often present in cells that are ‘resting’ or ‘sleeping’.

The drugs are getting us closer to finding a cure. You may need medication for a long time, but newer drugs may be easier to take and more effective.

This means you may still get to die of old age rather than from HIV.

It may also mean that you are still alive when we find a cure - and this is something good to aim for.

Don’t look at the drugs you start with now as a treatment that you will be taking forever.

Look at them as something you have to be really committed to for the next couple of years.

Take this new aspect of your life more seriously than anything else until you get it right.

 Produced by HIV i-Base

HIV treatment information for healthcare professionals and HIV-positive people