Topics on this page include the following; you can jump to them by clicking on the headings below:
- HIV – Cure or Treatment?
- Starting HIV Treatment
- Monitoring HIV Treatment
- HIV Drugs
- Side Effects
- Drug-drug Interactions
- Opportunistic Infections (OIs)
- IRIS in ART
- HIV Research
There is to date no cure for HIV. However, treatment is available that will stop people from becoming ill for many years. For someone who is newly diagnosed today in a timely fashion (that is to say, not diagnosed late), and who then takes their HIV treatment properly and consistently, then their life expectancy is expected to be very similar to that of the general population, and they can continue to lead healthy and fruitful lives. Modern HIV drugs are very effective, and much easier to tolerate than the older drugs – often, treatment will be in the form of one or two tablets, to be taken once a day. Side effects in most cases are very mild, and disappear after the initial few weeks of treatment. HIV is now regarded as a chronic but treatable condition – this does mean, though, that you will need to continue to take treatment for the rest of your life.
The main type of treatment for HIV is in the form of anti-retroviral drugs which aim to keep the level of HIV virus in the body at very low levels, and so protect the immune system from damage. These drugs are referred to as anti-retrovirals, or ARVs. It was found that to suppress the HIV virus in the body successfully, a combination of ARVs needs to be taken; typically, a combination of three ARVs is needed. If only one ARV is taken, then the HIV virus quickly becomes resistant to it, and the treatment becomes ineffective; by taking a combination of ARVs, this development of resistance can be prevented, and so treatment can remain effective for many tens of years. To be successful, though, ARVs need to be taken regularly and on time, without skipping doses. This is called adherence. Today, in the developed world, several ARVs may be combined into one tablet, to make them easier to take.
This type of treatment is often referred to as anti-retroviral therapy (ART) or combination therapy; or HAART (Highly Active AntiRetroviral Therapy); or cART (Combined Anti-Retrovirlal Therapy).
There are more than 20 ARV drugs available now, and HIV clinicians will be able to recommend an appropriate combination for each individual. Because the HIV virus mutates so rapidly in the body, different people may need different treatment – indeed, for HIV, there is no “one size fits all” treatment – treatment must in every case be carefully tailored to the individual’s needs. This applies not only to the specific choice of ARV, but also must take into account the individual’s reaction in terms of side-effects, and even the ability to take the drugs on time, every time.
2015 update – New treatment guidelines have been published by both the British HIV Association (BHIVA) and the World Health Organization (WHO). Both clearly recommend that all people living with HIV should start HIV treatment as soon as is practical.
The discussion below (under “older guidelines”) shows that previously, treatment was delayed until the CD4 count had fallen to a certain level. This is now no longer the case. In the UK, anyone living with HIV who understands the commitment of treatment and is ready to start should receive treatment, regardless of CD4 cell count.
Doctors should talk to their patients about the evidence showing that people who begin HIV treatment earlier have better long-term health outcomes than people who delay treatment. They should also discuss the evidence showing that treatment also substantially reduces the risk of passing HIV on to other people. Clinically, then, there are advantages to starting treatment as soon as possible. The decision to start treatment, however, rests with the person living with HIV.
HIV treatment is a life-long commitment. There is as yet no cure for HIV. Treatment will need to be taken every time, on time, in order to remain effective…if treatment is not taken regularly, resistance to the HIV drugs may develop, making them ineffective and potentially leading to life-threatening illness. You need to be sure that you can commit to this before starting treatment. Note that today’s HIV drugs are usually very easy to take, with minimal or very few side-effects, which usually go after a few weeks.
When a person is diagnosed with HIV, they may not immediately need to start HIV treatment. Starting treatment will depend on a number of factors, but principally, on the stage that HIV has reached in the body. This can be assessed by doing some clinical tests on blood samples from the patient. The two key tests are described below: they are the CD4 count, and the viral load. Other tests will also be done, for example to monitor liver and kidney function, but the key tests with regard to HIV itself are the two just mentioned.
The CD4 count is usually used to determine when a patient should start treatment. The tests measures the number of T-helper cells (in a cubic millemetre of blood), and is referred to as the CD4 or cell count. HIV attacks the human immune system by damaging and destroying T-helper cells. Someone not infected with HIV will typically have a CD4 count of between 500 and 1200 cells/mm³. When HIV is present, it will over a period of years start to reduce the CD4 count, typically by about 60-80 cells/mm³ per year. When the CD4 count gets low, below 200 cells/mm³, serious infections can start to occur; at very low levels, very severe and often unusual life-threatening infections can occur. In the UK, HIV treatment is currently typically started when the CD4 count falls below 350 cells/mm³. This may be revised at some point as more evidence from clinical trials is obtained. Some clinicians are beginning to think that starting HIV treatment sooner, say when the CD4 count falls below 500 cells/mm³, or indeed, starting treatment irrespective of the CD4 count, may preserve the immune system more, and offer patient benefits, but the results of these trials are not yet in. HIV treatment may be started sooner under certain circumstances – for example, co-infection with another illness such as hepatitis B or C or tuberculosis (TB), or for a woman, if she is pregnant. The decision of when to start treatment is an individual decision, to be made jointly by the clinician and the patient, and depends on a full clinical assessment of the patient.]
Once the decision to start HIV treatment has been made, then the choice of what ARV treatment regimen needs to be made. Before starting treatment in the UK, a resistance test should be done, to help assess what combination of ARVs should be used. This is because it is possible that the strain of HIV that an individual has may already be resistant to one or more of the HIV drugs – this is called transmitted resistance. Resistance can also develop if HIV drugs are not taken properly – this will be discussed later in the section on monitoring HIV treatment. In addition, all other drugs being taken for any other conditions – or recreational drugs, or herbal medicines – need to be fully disclosed and considered. This is because of drug-drug interactions: some drugs can affect the way HIV drugs work, often by making them less effective. In the light of all this information, the clinician will be able to suggest which ARV combinations may be suitable for treatment.
Once a person starts HIV treatment, it is essential that they adhere to their treatment. The term adherence means taking the drugs exactly as described – taking all of the medication at the right time and exactly as the directions state. It also means ensuring that there will be no interactions with other drugs being taken. This is extremely important in order to prevent the develop of resistance, leading to failure of the HIV treatment. The viral load test gives a measure of how effectively the HIV treatment regimen is working. Viral load refers to the amount of virus in the blood: if the viral load is high, this means that there is more virus present, and so will lead to more damage of the immune system (and usually, a lower CD4 count). The aim of HIV treatment is to reduce the viral load to as low as level as possible – called “not detectable” or “n/d”- and then keep it there for as long as possible.
For people starting treatment, the viral load will fall rapidly, and typically reaches n/d in 3 – 6 months. If the rate of viral load decrease is too slow, so that n/d is not reached, then it means that the HIV treatment is not working effectively. This may be because of poor adherence; to be successful, people need to aim for 95% adherence – that means, for example, missing no more than 1 dose in 3 months if on a once-a-day regimen. Or it may mean that the HIV is resistant to one or more of the ARVs in the treatment regimen. In any event, it is likely that a change in regimen will be needed if the viral load does not reach n/d, or does not stay n/d. Viral load tests do fluctuate with time, or they may be measurement errors, so viral load re-tests are usually done before any changes to the treatment regimen are made.
If the viral load can be reduced to n/d, then keeping it there is key to preventing the development of resistance. As long as the viral load is n/d (which typically means less than 50 or 40 copies/ml, depending on the viral load test used), then resistance will not develop, and the patient can stay on this regimen for many years (or decades). Good adherence is key to this.
Switching HIV treatment regimens may also be necessary for reasons other than a sustained increase in viral load (this is often called “virological failure”). Most people experience only mild side effects for the first few weeks of treatment, but for others, the side effects may be more severe and more persistent. If that is the case, and the side effects cannot be managed (by for example, taking loperimide to reduce diarrhoea), then the clinician will be able to suggest other, alternative HIV regimens which may be more easy to tolerate. It is important, though, to report all side effects to the clinician, and see how best to manage them, before considering a change in ARV regimen. Treatment switching should always be done with clinical advice and under carefully controlled conditions.
As well as monitoring your viral load, many other things are monitored regularly as well – some things every visit, others perhaps annually. We know now that having HIV, and being on HIV treatment, may make you slightly more likely to experience some conditions than the general population – for example, people with HIV are slightly more at risk of cardiovascular problems (strokes and heart attacks). So your doctor will monitor your cholesterol and blood fats to see if you are at higher risk, and may prescribe statins if necessary. Similarly, people with HIV are slightly more likely to develop type 2 diabetes, so your blood sugar will be monitored. And since HIV drugs have an impact on your kidneys and liver, these too will be monitored to ensure that there are no problems. This all might sound alarming, but the increased risks are small – and you will be very carefully monitored for any changes, so that if needed, action can be taken swiftly.
There are currently more than 20 approved HIV drugs in the UK, including some that combine two or more drugs in one tablet. Many more HIV drugs are available in the expanded access programmes and trials, and even more are still being developed in the research phase.
Most antiretroviral drugs have at least three names. It may be referred to by its research or chemical name, such as AZT. The second name is the generic name for all drugs with the same chemical structure; so AZT is also known as zidovudine. The third name is the brand name given by the pharmaceutical company, which for AZT (or zidovudine) is Retrovir. In addition, an abbreviation of the common name might sometimes also be used, such as ZDV, which is the fourth name given to zidovudine.
There are to date five classes of HIV drug, each of which attacks the HIV in a different way. The three main groups are:
- Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (often referred to as NRTIs, nucleoside analogues, or nukes)
- Non-Nucleoside Reverse Transcriptase Inhibitors (often referred to as NNRTIs, nNRTIs, non-nucleosides, or non-nukes)
- Protease Inhibitors (often referred to as PIs)
More recent classes are:
- Fusion or Entry Inhibitors (sometimes referred to as EIs)
- Integrase Inhibitors (sometimes referred to as IIs)
Usually, treatment requires three drugs from at least two classes. The most common drug combination given to those beginning treatment consists of two NRTIs combined with either an NNRTI or a “boosted” PI – most PIs require a booster to enhance their effect. The most commonly used booster is Ritonavir (in small doses). An example of a common combination is two NRTIs zidovudine and lamivudine, combined with the NNRTI efavirenz.
There are now several Single Tablet Regimens, such as Atripla and Stribild, where three or four drugs have been combined into one tablet, making it easier to take – you just need to take one tablet instead of three or four. There are also some Fixed Dose Combinations, such as Kivexa and Truvada – here, some drugs have been combined, but not enough to make a full treatment regimen, so they need to be taken with something else.
A chart listing most of the drugs used can be found here.
Almost every drug has some side effects. These unwanted effects are often mild, but sometimes, for some people, they can be severe or even life-threatening. Side effects for any drug vary from person to person, and in most cases it is impossible to predict how an individual will be affected. There may be some data for a drug which gives an indication of the likely side effects, and an estimate of the percentage of people experiencing these side effects, but it is almost impossible to say whether or not you will be affected in that way. Just because person A has experienced a side effect does not mean that person B will.
Many of the early ARVs used to treat HIV in the early years of the epidemic had severe side effects for most people, and the drugs were not easy to take – often, there would be many pills that needed to be taken at 4-hourly intervals. Fortunately, ARVs today are much easier to take – often just one or two tablets, to be taken once or twice a day. Also, the modern ARVs for HIV are much easier to tolerate – most side effects (if indeed any are experienced at all) are minor, affecting only a few people, and often only for the initial few weeks of taking the drug.
Nonetheless, for some people on HIV treatment, side effects can be an issue. Once started, antiretroviral treatment – HAART – must be taken every day for life. Every missed dose increases the risk that resistance will develop, and the drugs will stop working. It is therefore vital that people get all the help they need to eliminate or minimise the impact of side effects. There may be ways to lessen the impact, either by treating the side effects or, if necessary, by switching to alternative antiretroviral drugs.
The most commonly seen side effects are nausea, fatigue and diarrhoea. Often, one or more of these symptoms may appear shortly after starting an antiretroviral drug but then disappear within a few weeks as the body gets used to the drug. However, sometimes they do not go away; also, there are other side effects (again, mostly in older drugs) that take longer to develop and are persistent and irreversible – such as peripheral neuropathy (tingling, pain or numbness in toes and/or fingers) and lipodystrophy (re-distribution of body fat: either wasting of limb and facial fat, or accumulation of trunk fat, or both). Both peripheral neuropathy and lipodystrophy are rare now for people recently diagnosed and starting treatment on the newer drugs.
It is important, though, to be aware of the potential for side effects, and to monitor them and report them promptly to your clinician, particularly when they are affecting your quality of life. However, many of the side effect symptoms are rather non-specific, and may be caused by factors other than the HIV ARVs. It is important, then, for the clinician to try to determine what might be causing the symptoms – other causes might include another illness or infection, or stress, diet or other medication or drugs (including herbal treatments and recreational drugs) that might be being taken as well as the ARVs.
More detailed information can be found on the following sites:
Reading this material might be alarming! Remember, though, that many of these side effects are found only with the older drugs that are not typically used in the UK today; and also, even though the information about a particular side effect for a particular drug is reported in the literature, it does not mean that you will experience it! Usually, it is only a small percentage of people taking that drug that will see these side effects. However, it’s good to be aware of the potential, and be prepared to deal with it should it arise.
Due to effective HIV treatment, people living with HIV (PLWH) are living longer. Most PLWH can expect to live a near-normal lifespan, as long as they stay on succesful antiretroviral thereapy (ART). However, there are many medical conditions which are commonly experienced in older age and which may occur a little earlier in PLWH than in other people. Managing these medical conditions effectively, as well as continuing to treat HIV, is now an imporatn consideration.
The extra medical conditions (co-morbidities, in doctors’ language) include high blood pressure, heart disease, diabetes and cancer. It also includes depression, cognitive impairment, bone fractures and incontinence. Half of all people living with HIV will need to take at least one other long-term drug alongside their HIV treatment. Doctors will need to check that these drugs can be safely taken together. Some commonly-used drugs for treating some of these conditions other than HIV can interfere negatively with the anti-retroviral drugs used to treat HIV.
If you are on HIV treatment and you are also taking medicines for another health condition, it’s important to check for drug-drug interactions. Each doctor you see needs to know about all the medicines you are taking.
This is a complex area. Many commonly-used medicines interact with HIV drugs. These include:
- Antifungal drugs with names that end in “-azole”
- Some antibiotics (names end in “mycin”)
- The antacid cimetidine (Tagamet)
- Some drugs that prevent convulsions, including Dilantin and Tegretol
- Drugs to control heart rhythm
- Sedatives, including Versed and Halcion
- Drugs to thin the blood, including warfarin (Coumadin)
- Methadone and buprenorphine
- Pain killers derived from opium
- Drugs to treat erectile dysfunction, such as Viagra
- Drugs used to treat tuberculosis, especially rifampin
This list is not complete, and not all of these medicines interact with every type of HIV drug. If you are receiving any of these types of medicine, as well as your HIV drugs, your GP or HIV consultant needs to check that the medicines can be taken together safely.
Herbal remedies and recreational drugs can also interact with some HIV drugs. Examples include ecstacy (MDMA), GHB, crystal meth and speed. Viagra and poppers also interact with some HIV ARTs, as do anabolic steroids and methadone. Some herbal remedies can also cause problems with some HIV drugs, though research on this is limited. St John’s Wort is in particular known to cause problems with some HIV drugs.
When discussing drug-drug interactions with your clinicians, you need to include both recreational drugs and herbal rememdies in your review of drugs used.
If HIV is untreated, then over time, the immune system becomes more and more damaged. A measure of this is the CD4 count, which for uninfected people is typically in the range 500 – 1200 cells/mm³. When the immune system is severely damaged (typically with a CD4 count less than 200 cells/mm³), people are vulnerable to infections and malignancies that are called “opportunistic infections” or OIs, because the infections take advantage of the opportunity offered by a weakened immune system.
When the immune system is weakened (CD4 less than 200 cells/mm³), people can develop tuberculosis (TB), bacterial pneumonia, herpes zoster, staphylococcal skin infections and septicaemia. These are diseases that people with normal immune systems can also get, but with HIV they occur at a much higher rate. When the immune system is very weak due to advanced HIV disease (CD4 count less than 50 cells/mm³) opportunistic infections such as CMV, toxoplasmosis and cryptococcosis can develop. Many of these OIs are very serious and can lead to death.
Thanks to the effective HIV treatment available today, though, problems with OIs in the UK are now quite rare. If you are on an effective HAART regimen, then it is quite unlikely that your CD4 count will fall below 200 cells/mm³, and problems such as those mentioned above are most unlikely to arise.
The aim of ART (Anti-Retroviral Therapy) in HIV patients is to restore the damaged immune system. A measure of the health of an individual’s immune system is given by the CD4 count. In healthy individuals without HIV, this is typically between 800 and 1200. When someone is infected with HIV, the CD4 count steadily falls. A CD4 count of less than 200 means that a patient is at risk of OIs (Opportunistic Infections); a count of less than 50 is very concerning and can lead to life-threatening conditions. Fortunately, ART leads in nearly every case to rises in the CD4 count, and for someone with HIV, a successful ART regimen can restore the CD4 count to virtually normal levels.
However, in a small percentage of cases, usually in cases where ART is started in individuals with a very low (less than 50-100) CD4 count, an unusual condition can arise, known as IRIS (Immune Reconstitution Inflammatory Syndrome). It may, though, in very rare cases occur even at relatively high CD4 counts. Typically, symptoms of IRIS will occur after 4-8 weeks of ART, though again, in rare cases, it may occur earlier, or much later. As the patient’s immune system starts to recover, thanks to the start of ART, in the case of IRIS, it “over-reacts”. This means that infections which had been lying dormant, or under control, can suddenly flare up; also, conditions associated with inflammatory responses such as rheumatoid arthritis can be triggered. For patients with very low CD4 counts, the infections triggered might be relatively minor and transient (such as herpes or warts); however, the infections can also be very serious, such as tuberculosis (TB), Kaposi’s Sarcoma (KS), CMV (cytomegalovirus), meningitis and more.
Clinicians will be well aware of the possibilty of IRIS in patients starting ART with very low CD4 counts. For minor problems with IRIS, treatments are available to help deal with the problem; in rare cases, serious conditions as a result of IRIS can arise and require urgent additional treatment. In all cases, though, starting or staying on ART is the advised course of action, and except in severe cases, patients should remain on ART.
It should be remembered that cases of IRIS are relatively rare in the UK, and usually only seen in patients starting ART with very low CD4 counts. For the vast majority of people, IRIS as a result of ART is not an issue.
There has been a huge effort into finding ways to treat and cure HIV. The first cases of HIV in the developed world were in the early 1980s, and a lot of work was done to understand just what was really causing the illnesses that were initially unexplained. We now know that the cause is HIV, and we can test for it; this was not really understood until the mid 1980s. The focus then shifted to finding a cure, and treating the HIV infection. Progress on finding a cure has been disappointingly slow, and to date, there is no cure, and no signs of a cure in the near future. Progress on treatment, though, has been remarkable. By the late 1980s, drugs were appearing that could prolong the life of someone with HIV; however, many of these early drugs were themselves very unpleasant to take, with severe side-effects. The situation improved in the early 1990s, and a milestone was the introduction of combination therapy in 1996. Newer drugs increasingly had better side=effect profiles, and today, there is a wide range of drugs, with mostly minor and transient side-effects.
All of this progress has come from careful studies and clinical trials, primarily done by the pharmaceutical industry. Even today, a lot of new developments continue to occur, and as more is learnt, so HIV treatment is modified to incorporate the new knowledge into clinical practice.
There are some useful sites if you are interested in following the very latest developments in HIV. The source material is of course in the main scientific journals such as Nature, The British Medical Journal, and AIDS. These, though, can be difficult for a layman to understand – these articles are written by scientists and clinicians for scientists and clinicians, and so are full of medical terms, jargon and lots of detail. There are other sites, though, where these detailed accounts are made more understandable for the average reader. These include: