FREQUENTLY ASKED QUESTIONS ABOUT TREATMENT
Use the links below to guide you through frequently asked questions about combination therapies how they work and what a person diagnosed with HIV can expect. For more detailed information refer to your health care provider or the Department of Health in your area.
What's Combination Therapy? | How do the drugs work? | How can we tell they work?| What's Viral Resistance? | How effective is Combination Therapy? | Is this a cure? | What drugs are prescribed? | Which combination is best? | When should I start? | Side Effects | Difficult to take? | Availability in Bermuda | What's the future?
The term 'combination therapy for HIV' means taking several different drugs to slow down and stop reproduction of the virus. These drugs are called anti-virals anti-HIV or anti-retrovirals because they attack the virus directly. Research shows this is currently the most effective way we have to treat HIV.
Antiretroviral drugs target specific stages of the HIV virus' life cycle preventing it from reproducing itself (replicating). There are three main classes of anti-HIV drugs each attempting to disable the virus at a different stage of its life cycle:
nucleoside reverse transcriptase inhibitors (NRTIs) sometimes called 'nukes'. They are: AZT or Retrovir ddC or Hivid ddI or Videx d4T or Zerit 3TC or Epivir and abacavir or Ziagen.
non-nucleoside reverse transcriptase inhibitors (NNRTIs) delavirdine or Rescriptor efavirenz or Sustiva and nevirapine or Viramune.
protease inhibitors: indinavir or Crixivan saquinavir soft gel or Fortovase saquinavir hard gel or Invirase ritonavir or Norvir nelfinavir or Viracept amprenavir or Agenerase.
It has been shown that combining three or more drugs which attack HIV in different ways has a more powerful effect on viral activity (measured by viral load) than taking one drug alone. In some cases viral load can be lowered to an undetectable level; this does not however mean that the virus has been eliminated only that its activity is too low to be measured by current tests.
How can we tell if the drugs are working?
Two different blood tests are used to monitor the progress of the virus and these are especially important for anyone beginning or taking anti-HIV therapy:
CD4 count: CD4 cells are white blood cells in the immune system which are targeted by HIV. A CD4 count measures the number of these cells contained in a cubic milli-metre of blood. The lower your CD4 count the more damage your immune system has sustained from HIV infection. It is important to have a CD4 count at regular intervals to gain an accurate picture of how your immune system is functioning because one particularly low count could be due to factors other than HIV e.g. tiredness or stress. The CD4 count is also sometimes referred to as a T-cell count.
Viral load count: this tests the amount of HIV in your blood. The higher your viral load the more virus there is in your blood. It is important to take more than one test with a gap between them to see if your viral load is growing or stable; a rising count means that the virus is becoming more active and more dangerous.
A series of tests which showed that your CD4 count was rising while viral load was falling would be an indication that anti-HIV therapy was working well. However if the results were reversed it could well indicate that HIV has developed resistance to one or more of the drugs in a combination and the virus is beginning to replicate (see Drug resistance). This could be a time to consider changing therapy.
Every time HIV reproduces itself (replicates) to hijack a host cell and generate new virus there is a chance for a mistake to be made. These mistakes or mutations produce changes in the genetic code of the virus which give rise to a new virus with a slightly different character. Since HIV is estimated to infect about 10 million cells each day there could be up to this number of possible mutations each day. Unfortunately some mutations can make the virus immune to some anti-HIV drugs. To prevent resistance from developing doctors believe all virus replication must be suppressed as much as possible and that viral load levels should be kept as low as possible for as long as possible.
How effective is combination therapy?
Combination therapy can successfully reduce the level of HIV in blood and has had a dramatic effect in improving the health and life expectancy of people with HIV. However we do not yet know the long-term effects of these drugs or whether the improvements people are experiencing can be sustained in the future.
Over the years that these drugs have been readily available many who were seriously ill have returned to good health and in many cases returned to work. In some people however the virus can develop resistance and cross-resistance to the drugs (cross-resistance means that the virus will be resistant to other drugs in the same class of antiretrovirals as well as to the actual drug used). A minority of patients are unable to benefit from the current anti-HIV drugs.
Does this mean there's now a cure for HIV?
No. Despite the hype nobody has yet demonsrated that these drug combinations can completely eliminate HIV from the body or suppress HIV to such low levels that it cannot cause long-term immune system damage.
What combinations of drugs are prescribed?
Currently combinations of at least three anti-HIV drugs (triple therapy) are the standard of treatment. This combination is usually composed of two nucleoside reverse transcriptase inhibitors (NRTIs) or 'nukes' and one protease inhibitor however in some patients depending upon their viral load at start of treatment or their concerns about possible long-term side effects of protease inhibitors the triple therapy consists of two NRTIs and a non-nucleoside reverse transcriptase inhibitor (NNRTI). In some circumstances a four drug combination is prescribed which usually consists of two NRTIs and two protease inhibitors. Other combinations are currently on trial.
Which combination is the best?
None of the research conducted so far has revealed a definitive 'best' combination of drugs. Each has its positive and negative points and anyone considering treatment needs to discuss the most suitable drug combination with their doctor. They should consider a number of factors including potential side effects current state of health and how taking the drugs will fit into their lifestyle. What we can say is that the best combination for anyone is the one that best fits their lifestyle and achieves maximum suppression of HIV.
When should you start therapy?
It is not yet clear whether there is a 'best time' to start antiretroviral therapy. This is a decision which a person with HIV must make for themselves in consultation with their doctor. It will depend on a variety of medical practical and emotional issues. However the goal is to start therapy early enough to prevent irreversible damage to the immune system so most guidelines recommending starting therapy when your CD4 count falls below 350.
Combination therapy involves taking powerful drugs many of which have strong side effects. Some side effects may last a relatively short period of time such as nausea diarrhoea and headaches; others may be longer term or more dangerous. Some effects can be reduced gradually increasing the dose (as with ritonavir) or taking other drugs to treat side effects.
If a person experiences serious side effects such as problems with their liver or pancreas they may need to consider changing treatment. There is a growing body of research showing that long-term use of certain anti-HIV drugs can lead to metabolic imbalances in some patients. This has encouraged some people to change their combination in order to avoid certain drugs.
Is combination therapy difficult to take?
Combination therapy needs to be taken in accordance with instructions at the right time and in the right dose. This is because a person needs to maintain a minimum level of each drug in their bloodstream for the therapy to be effective. If this level drops the virus will start replicating and may have the opportunity to develop resistance.
Adherence to or compliance with combination therapy is complicated by the large number of pills which need to be taken often at different times of the day and with different instructions about food and drink. Some people may forget to take the pills or be too embarrassed to take them in a public setting or may not have been told how important it is to take the proper dosage. There are a growing number of support groups and resources for people on combination therapy.
How easy is it to get these drugs?
Drugs which have been approved by the FDA should be available to anyone in Bermuda with HIV who wants to take them. Access to treatment should not depend on where you live how informed your doctor is or the budget priorities of the local Department of Health. Additional services are available i.e. counseling weight management and nutrition management through a special programme for indigents. Only your doctor or the staff at the Victoria Street Health Centre can refer you to these services.
Ultimately the aim of HIV therapy should be to eradicate the virus and rebuild the immune system. However current approaches to therapy cannot directly pursue this objective; rather they aim to maintain viral load levels at below the limits of detection using multi-drug therapy. The assumption is that stopping viral replication will prevent resistance developing and help to regenerate and reconstruct the immune system. Some experimental treatments are currently combining antiretroviral therapy and immune boosters which are a type of therapeutic vaccine.
Thus the strength of antivirals is critical to therapy success. Regimens with response rates less than 100% can never be accepted as ideal therapy. Individuals who have difficulty adhering to therapy will find that their therapy fails earlier than those who can adhere.
For the future routine drug resistance testing may be introduced as a key tool to help clarify the prime cause of treatment failure. Also the development of more accurate viral load measurements with lower detection limits is showing us that not all patients are able to respond fully to a particular combination.
These patients may subsequently progress faster to illness than those whose virus can go below detection limits. There are many new antiretroviral drugs in different stages of clinical trials and approval. Researchers are also working on making the drugs easier to manage e.g. combining two different drugs into one pill reducing the frequency of dosing or making slow release formulations.