The goal of anti-HIV treatment is to reduce the amount of HIV in the body. The treatment should stop you from becoming ill for many years. Sometimes the antiretroviral therapy works without any major problems or setbacks, but sometimes there can be difficulties.
The antiretroviral drugs have not been available for very long, and despite ongoing research and development, there are some problems associated with them. Here you can find information about the issues that you may face when continuing your antiretroviral treatment.
Drug resistance
Antiretroviral drugs slow down the replication of HIV in the body. However the drugs cannot stop the replication completely and so some HIV is able to survive despite ongoing treatment.
When HIV replicates it often makes slight mistakes, so each new generation of HIV differs slightly from the one before. These tiny differences in the structure of HIV are called mutations. Some of the mutations occur in the parts of HIV which are targeted by anti-HIV drugs. So although you have some HIV that continues to be affected by the drugs, you have other strains of HIV that are not affected by the anti-HIV drugs as effectively as before. This HIV is called drug resistant HIV, and it is then able to replicate unaffected by the drugs.
When someone has drug resistant HIV (commonly referred to as drug resistance), the amount of HIV in the blood rises and the risk of the person becoming ill increases. Drug resistance is one of the main reasons why antiretroviral treatment fails. If resistance to the current drug treatment develops, this usually means that the drug regimen needs to be changed.
The viral load test can reveal developing drug resistance. Normally when treatment is started, the viral load drops to the undetectable level. A sign of developing resistance is if the viral load increases. In some countries, the resistance to certain drugs can be monitored by using specific resistance testing: genotypic and phenotypic testing.
Avoiding resistance
There are certain things that can be done to minimise the risk of developing drug resistant HIV. In the first place, if the drug combination is strong then there is less risk of resistance developing. This usually means taking a combination of 3 or 4 drugs.
Regular viral load testing is also important. The viral load test can indicate if you are developing a drug resistant strain of HIV. If the drug combination is working, the viral load should be undetectable. If the viral load has increased, this can be a sign of growing drug resistance.
Taking medication exactly as prescribed is another very important part of avoiding resistance. Missing doses or not taking them on time lowers the amount of antiretroviral chemicals in your body and the virus is not properly suppressed. Then the virus is able to replicate itself faster and there is an increased risk of it becoming resistant.
Cross-resistance
Resistance to some antiretroviral drugs can limit which treatment options are available to you in the future. If HIV is resistant to one drug, it will sometimes be resistant to similar drugs in the same group. This is called cross-resistance and it means that some anti-HIV drugs will not work even though you have not used them before.
Cross-resistance is a particular problem if a person develops cross-resistance to a whole group of drugs. For example, if a person has developed a resistance to one of the non-nucleoside drugs, there is a risk that none of the other non-nucleosides will be effective.
Drug interactions
The interaction between certain anti-HIV drugs and other drugs, both pharmaceutical and recreational, can alter the effectiveness of antiretroviral therapy. The main risk is that interactions between drugs may lower the amount of anti-HIV drugs absorbed allowing low level HIV replication to occur, which may increase risk of drug resistance. If you are taking drugs other than prescribed anti-HIV therapy, always read the instructions or consult your doctor.
Pharmaceutical drugs for treating opportunistic infections are among those that may have undesirable interactions with antiretroviral medication, for example the tuberculosis treatment rifabutin should usually not be used with the protease inhibitor saquinavir or the NNRTI delavirdine.
Interactions between recreational and antiretroviral drugs have resulted in several deaths in recent years because of the potentiation (boosting) effects that antiretrovirals have on the recreational drugs. Minimal solid research has been carried out in this area and little is known about how the body processes recreational drugs. The safest action is not to mix these drugs with antiretrovirals at all.
Side effects
Drugs are generally licensed and tested to treat specific illnesses. What are referred to as side effects happen when the drugs affect the body in ways other than those intended. Most of the anti-HIV drugs have known side effects, but this does not mean that everyone who takes them will experience side effects. Generally, you cannot predict if you are likely to experience side effects or not. Some people only experience the side effects mildly and find them easily manageable. But for some people the side effects occur so strongly that they have to consider other alternative drugs.
The most common side effects are nausea and feeling tired. Side effects are often referred to by the grade of the effect, and the grades range from mild to moderate to severe to life-threatening. For example, it is considered a mild side effect if a person has 2–3 vomiting episodes a day. Life-threatening side effects such as extreme limitations in daily activity and hospitalisation are rare, but are still threats to some.
When drugs are developed they go through clinical trials. A clinical trial is a study with people to test how well the new drugs or treatment works and how safe it is. Some long-term side effects may not be noticed in the clinical trials. It is hard for the researchers to draw consistent information on side effects in clinical trials, since people have different treatment histories, general health and tolerability levels. Therefore, some side effects only become apparent after the drugs have been approved and have been used by more people over a longer period.
Since HIV is a life-threatening infection, there is a constant need for new drugs. Sometimes it is important to get a drug on the market despite known side effects. Many patients and health professionals agree that the anti-HIV drugs are far from perfect and the tolerability and side effects of the drugs need to be vastly improved.
It can be useful to find out about the possible side effects that particular drugs have, before you start treatment. The side effects often get better after you have been on the treatment for a little while, as the body then starts to adjust to the anti-HIV drugs. Some people use alternative therapies and medications with the combination therapy to ease the side effects. For example, some people find taking peppermint eases their feeling of nausea. Sometimes the side effects do not diminish over time, and in some instances one or more of the drugs in the combination can be changed to reduce the side effects. If you feel that the side effects are too much to cope with, you should always seek help from your doctor before changing or stopping your regimen.
Adherence and side effects
The term adherence means taking the drugs exactly as described. Adherence is a very important part of anti-HIV treatment. Often experiencing side effects makes adherence difficult. Your doctor might be able to give you some treatment to help with the most common side effects such as nausea and diarrhoea. As adherence is such an important part of treatment, it is important to monitor closely the effect that side effects have on your adherence. If side effects are affecting adherence, you must tell your doctor.
Changing treatment
A drug combination can fail for a number of reasons including:
- The combination of drugs was not strong enough
- The drugs were not absorbed properly by the body
- Drug resistance
- Strong side effects
- Poor adherence.
There are two main reasons why anti-HIV treatment sometimes needs to be changed.
Firstly, a change of treatment is needed when the antiretrovirals fail to work and slow down the replication of the virus in the body. Increased viral load or an HIV-related illness are signs of failing anti-HIV treatment.
Secondly, sometimes side effects are so strong, intolerable and even life-threatening that the treatment must be changed.
Monitoring the viral load carefully is an important part of treatment. There are different opinions about the "right time" to change the treatment if your viral load is rising. Some doctors recommend changing the treatment as soon as the viral load starts to rise. Others recommend monitoring the overall trend of the viral load before making a decision to change. Changing the drugs earlier rather than later could mean running out of treatment options more quickly. But changing later means there is a danger of developing resistance to certain drugs. This can seriously limit your future treatment options. The changes that can be made to the drug regimen will depend on the drugs already being used, the CD4 count and your general health.
The anti-HIV drugs work best when used the first time. This is one of the reasons why it has to be considered carefully whether a change of treatment is necessary or not. The combination of anti-HIV drugs other than the first or second treatment is called salvage therapy. It is also referred as second-line, third-line or rescue therapy.
Many people start their salvage therapy with much higher levels of viral load than when they started previous treatments. This puts more pressure on the new combination to work. Each combination used lessens the chance of maintaining a low viral load because of the possibility of developing resistance to the drugs. The choice of new treatment should always depend on what caused the previous one to fail.
If you have an increased viral load, strong side effects or need to change your anti-HIV treatment for any other reasons then always contact your doctor before taking any action.
Structured Treatment Interruptions (STIs)
A Structured Treatment Interruption (STI) or drug holiday is when someone stops taking anti-HIV treatment temporarily. People take treatment interruptions for a variety of reasons, such as side effects, ineffectiveness of the drugs and psychological issues. STI does not mean skipping or stopping your medication randomly, but taking a break from your drug regimen with a planned timescale, close monitoring and help from your doctor.
In theory, STIs can have benefits such as reducing toxicity, improving quality of life and lowering the cost of medication. Enjoying a drug-free period may also have some psychological benefits such as increased adherence when returning to treatment.
In recent years a series of studies have cast doubt on the safety of STIs. The most important of these was an investigation known as the SMART trial, which involved more than 5,000 patients in 33 countries. Volunteers in the SMART trial were randomly assigned to two groups. Members of the first group took treatment continuously, while the others took treatment only at times when their CD4 counts were very low. The SMART trial was ended in early 2006 because patients in the treatment interruption group were significantly more likely to fall ill or die.
The main risks of taking a treatment break are that the viral load will rise and the CD4 count will drop, increasing the risk of illness. Also, stopping and restarting the treatment can make it easier for the virus to develop resistance to the anti-HIV drugs. This is because some of the drugs remain in the body longer than others, so if a treatment interruption is not carefully managed then it can result in temporary "monotherapy", which makes it much easier for the virus to develop resistance.
The results of the SMART trial do not necessarily mean that all STIs are unsafe. Some studies have suggested that other types of STI might be as effective as continuous treatment in certain circumstances, though the evidence is not yet conclusive. If you are considering a treatment interruption or stopping your treatment then always talk to your doctor first. Taking unsupervised treatment breaks can do more harm than good to your health and can limit your future treatment options.
The need for safer sex
Unprotected sex puts both you and your partner at risk. HAART suppresses HIV but it doesn’t stop transmission, even when the viral load is undetectable. Unprotected sex with an HIV positive partner is not a risk-free activity; there are many different strains of HIV and it is possible to become infected more than once, which can complicate treatment. People on HAART should take as much care to minimise the risk of HIV transmission as they did before starting treatment. This is also very relevant for couples in which only one of the partners is HIV positive for prevention and family planning reasons.
Note: This information is cross-posted and slightly adapted from AVERT.org in order to emphasize some aspects refering particulary to Moldova. For more details, visual adds, updated information and primary sources, please visit AVERT.org web page.
Sources
- Continuing HIV Treatment //avert.org