Antiretroviral treatment

Although there are other factors that can help to keep a person with HIV infection well for many years, eventually it becomes necessary to take antiretroviral drugs in order to lengthen a person’s life.

Antiretroviral drugs work directly on HIV and slow down its multiplication. This in turn slows down the loss of CD4 T-cells that the virus destroys, and thus slows down further damage to the immune system or even allows the immune system to recover to some extent.

Controlling HIV infection and limiting damage to the immune system results in weight gain and improvement in general health, fewer opportunistic infections, less need for other medications and less time in hospital.

The purpose of antiretroviral therapy
Although antiretroviral therapy (or ART) is not a cure for Aids, the purpose of anti-retroviral therapy is to:

  • reduce the HIV viral load as much as possible - preferably to undetectable levels - for as long as possible (Virological goal).  
  • assure that less damage will be inflicted on the immune system, so that the patient will experience an improvement in his/her immune functioning and to delay the onset of Aids (Immunological goal).  
  • enhance quality of life and reduce opportunistic infections (Therapeutic goal).  
  • reduce the impact of HIV transmission in the community (Epidemiological goal).

The down sides and limitations of taking antiretroviral treatment:

  • It usually requires a fairly complex medication regimen: several different tablets must be taken at different times every day, some with food and others when the stomach is empty. Some tablets must be taken at exactly the correct times of day or they will fail.  
  • Often the drugs have unpleasant side-effects such as nausea and headache.  
  • The drugs are very expensive and need to be taken for the rest of a person’s life to control HIV infection, although they will never cure it. Several treatment changes will usually be required in the course of a person’s life with HIV. Therefore, you must be motivated and dedicated to take the treatment successfully.  
  • The virus can never be completely eradicated from the body. A reservoir of infected cells persists even in the absence of viruses in the blood, and its replenishment continues even during treatment.  
  • HI viruses use Memory T cells where they build up a latent reservoir. These latent cells can live for 44 months or longer and eradication of viruses from these cells are simply not possible.  
  • Active infected CD4 cells die and the viral pool in the latent T cells allows for a rebound of HIV.

Three Groups of Antiretrovirals
At the moment, there are three main types of drugs available to treat HIV. These three groups of drugs work against the virus in different ways, at different points in the growth cycle of the virus.

Counting up the different drugs from the three groups, there are about 16 different drugs available to treat HIV infection right now.

The function of ART is to protect activated CD4 cells - that is CD4 cells that are infected by the HI virus, and are now being used to make new viruses. HIV uses enzymes to replicate itself inside CD4 cells. Antiretroviral drugs act by blocking the action of these enzymes.

1. Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
These drugs are usually the first choice for HIV treatment and the backbone of HIV treatment.

The Reverse Transcriptase Inhibitors disturb the life cycle of the HI virus by interfering with the reverse transcriptase enzyme in the replication of the virus. The virus is no longer able to change its RNA into viral DNA.

NRTIs are: (with the proper name of each drug listed first, followed by the manufacturer’s “trade name” in brackets).

  • AZT or zidovudine (Retrovir)  
  • 3TC or lamivudine (Epivir)  
  • DDI or didanosine (Videx) etc.

2. Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

  • Nevirapine (Viramune)  
  • Efavirenz (Stocrin)

3. Protease Inhibitors
The Protease Inhibitors interfere with the formation of new viruses in the life cycle of the virus by blocking the protease enzyme from allowing the assembly and release of viable particles of HIV from the infected cells. PIs are:

  • Indinavir (Crixivan)  
  • Ritonavir (Norvir)  
  • Saquinivir (Invirase) etc

When to start treatment
The correct time to start antiretroviral treatment is a difficult decision, even among medical specialists. In general, it is agreed that it is preferable to start treatment before there is too much damage to the immune system, that is while the CD4 cell count is still at a moderate level such as 350 cells/ul.

It is also agreed that a person with the signs of Aids should start treatment. On the other hand, it may also be valuable to treat a person with very early (“primary”) HIV infection, at least for some time. There is evidence that controlling the virus early on means that it will not multiply to such high levels later on.

The choice of treatment may often be limited by what a person can afford, or what a particular treatment programme can offer. There are some rules that have to be followed for successful use of the drugs.

Why triple therapy?
One should never take one drug alone (“monotherapy”). This is because HIV will very quickly become resistant to one drug on its own, and so that drug will become ineffective and cannot be used for ongoing treatment.

However, if two or more drugs are used together the virus can only multiply very slowly and will take much longer to become resistant to any one of the drugs. Therefore, at least two drugs should be taken together (“dual therapy”), and preferably three (“triple therapy”).

For optimum viral suppression, triple therapy (or HAART - highly active antiretroviral therapy) is recommended, such as two NRTIs and one PI.

Some drugs work against each other, or cause the same bad side-effects and so should not be taken at the same time. Other drugs help each other and so they are good to combine.

From this it is apparent that antiretroviral treatment is complicated and so should be prescribed by a healthcare provider who is experienced in managing HIV. There are also guidelines on antiretroviral treatment available, such as World Health Organisation (WHO) guidelines and the guidelines of the South African HIV clinician’s society.

Can HIV be eliminated completely from the body?
HIV can unfortunately not be eliminated completely from the body. Because the virus remains latent or dormant in Memory T cells, it can easily become re-activated and infect CD4 cells.

When a person is on antiretroviral treatment, virus tests often show that the viral load is “undetectable” in the blood. It means that the viral load is so low that it cannot be detected with the kind of blood tests available to us. It does not mean that there are no more viruses in the body. Once antiretroviral therapy is discontinued, viral replication usually resumes and viral loads begin to rise again.

Practical guidelines

To take ART is not an easy option!
Therapy should be individualised: ART is not suitable for every person. Patients should be educated about the risks, benefits and demands, they should be committed to adhere to the medication for life, they should be able to take care of their health, and go for laboratory tests (CD4 counts and viral loads) regularly.

Side-effects should be monitored, harmful drug interactions should be monitored (e.g. St Johns Wort prevents absorption of some antiretroviral medications), absorption and tissue distribution should be monitored by taking the meds correctly - some with food, others on an empty stomach, some with lots of water, others with fatty foods.

Drug adherence is extremely important, for two reasons:

  1. ART will fail completely if not taken correctly and consistently: If ART is taken with more than 95% adherence, it is 81% effective; If adherence is less than 70%, it has an effectivity of 6%.
  2. Drug resistance is one of the major problems if patients do not adhere to the medication. Drug resistance occurs when the drugs cannot protect the CD4 cell any more. The virus then breaks through and infects the cell.

Note definition of resistance: it is not the person who develops resistance, but the virus that develops ways to resist the drugs, so that drug will not work in future.

Possible side-effects:
A person using ART must be carefully monitored. Some of the more serious side-effects include:

  • Lipodistrophy (change in fat distribution - shoulders and neck)  
  • Osteoporosis  
  • High cholesterol  
  • Metabolic disturbances (insulin resistance)  
  • Stephens-Johnson syndrome (Nevirapine) - ulceration in oesophagus, looks like chickenpox, causes “burns”, oedema. First signs: fever, rash, sore throat.

Provided by ArmMed Media
Revision date: June 18, 2011
Last revised: by David A. Scott, M.D.