An Introduction to Antiretroviral Therapy

While research is ongoing into new treatments for HIV/AIDS, and the effects of alternative therapies, for now the most effective treatment for HIV/AIDS is what is known as antiretroviral therapy (ART).

What Is Antiretroviral Therapy?

Antiretroviral therapy (ART) uses 2 or 3 (usually 3) antiretroviral medications to prevent HIV from replicating. There are five kinds of antiretroviral medication:

AZT was the first antiretroviral medication.

Nucleoside/Nucleotide Reverse Transcriptase Inhibitors – HIV reproduces itself inside cells by copying its RNA. NRTI drugs such as AZT work by interfering with transcriptase, a chemical that is an important part of this copying.

• Non-Nucleoside/Nucleotide Reverse Transcriptase Inhibitors – The NNRTI drugs also interfere with transcriptase, though they to it in a different way than NRTI drugs.

Protease Inhibitors – Protease is also used by HIV when it copies itself, and PI drugs stop the protease from working properly.

Fusion or Entry Inhibitors – these medications stop HIV from entering the immune cells

Integrase Inhibitors – Integrase is an enzyme that HIV uses to insert its genetic code into cells to be reproduced. These drugs keep the integrase from working, so the HIV can’t complete the insertion.

ART usually uses three of these drugs in combination, most often 2 NRTI medications, and one from another group. Taking multiple ARV medications is sometimes called combination therapy. Up to four ARV medications are used. Using four ARVs is referred to as Highly Active Antiretroviral Therapy (HAART).

Why Take Multiple Antiretrovirals?

Almost every time HIV reproduces, some mistakes get made in the copying. Eventually one of these ‘mistakes’ lets the virus fight back against one of the medications. This is called being resistant to the drug. The fewer times HIV copies itself, the fewer mistakes get made, and the less likely there are to be ‘mistakes’ that let the virus resist the medication. Once HIV becomes resistant to a medication, that medication won’t work to keep viral loads down, and AIDS will start progressing more quickly.

Taking just one ARV won’t stop HIV from copying itself as well as taking multiple ARVs. So when it is possible, people with HIV/AIDS on ART should take multiple ARVs to reduce the possibility of the virus becoming resistant to one or more of the medications.

When Should ART Be Started?

In places where the equipment to test CD4 counts is available, starting ART is based on how low CD4 counts are. CD4 is the name for the immune cells that coordinate the body’s immune response. When there are too few CD4 cells, the body can’t protect itself. Since HIV attacks CD4 cells, the number of CD4 cells drops as HIV progresses.

When CD4 counts can be tested, the World Health Organization (WHO) says that ART should be started when CD4 counts fall below 350 cells in a cubic millimeter of blood (<350 cells/mm3). In the United States, the official recommendation is that ART should be considered when CD4 counts are between 500 and 350 cells/mm3, and should definitely be started when counts fall below 350 cells/mm3.

When it isn’t possible to measure CD4 counts, WHO has developed a recommendation based on clinical stages of HIV/AIDS. WHO recommends starting ART as quickly as possible once the signs and symptoms of HIV reach stages 3 or 4.

Isentress (raltegravir), an integrase inhibitor. One of the newest kinds of ARV.

The two main exceptions to this recommendation are pregnant women and children with HIV/AIDS. Pregnant women who have not yet started ART should start it during pregnancy to prevent transmission of the virus to their baby. Without ART the transmission rate from mother to child is as high as 1 in 4 babies born with HIV, with ART the transmission rate drops to less than 2 in 100 babies born with HIV. When children have HIV it is recommended they start ART treatment as soon as possible.

Once ART is started, it can’t be stopped. A person with HIV/AIDS who is taking antiretroviral medication will need to continue taking it for the rest of their life.

What Happens if ART Stops Working?

A good ART combination will reduce viral load to undetectable levels (less than 50 copies of the virus per mL). Unfortunately, undetectable doesn’t mean ‘gone’. The virus is still there and still reproducing, just much more slowly. Eventually, it will make a copy that is resistant to one or more of the ARV medications.

Once HIV develops a drug resistance, the viral load will rise, and CD4 counts will start dropping. In places where it isn’t possible to test viral load or CD4 count, the resistance will result in a person with HIV/AIDS developing clinical symptoms of further stages of HIV/AIDS.

When it is clear that a resistance has developed, it is necessary to switch to a new combination of ARV medications.

What are Side Effects of ART?

Different antiretroviral medications have different side effects, but some side effects are common to most ARVs. Side effects can be divided into two categories: short term side effects, which go away after the body gets used to the new medication, and long term side effects, which may only start after taking the medication for a while, and often get worse over time.

When it is possible to identify which medication is causing which side effect, it may be possible to switch to a different ARV if the side effect is more than a person can comfortably live with. However, it often isn’t possible to tell which medication is causing a specific side effect, and many secondary infections common to HIV/AIDS have symptoms similar to ARV side effects.

Common side effects include:

• Diarrhea

• Nausea and Vomiting

• Rash

• Lipodystrophy (gaining and losing fat in unusual ways)

• Lipid abnormalities – lipids are fat based molecules that are important to the body’s function. Two well-known lipids are LDL and HDL cholesterol. Changes in the amounts of these lipids caused by ARVs can lead to heart problems.

What Happens if a Dose Is Missed?

It is important to adhere as closely as possible to the recommended schedule for ART. Studies have shown that if the medications aren’t taken appropriately at least 95% of the time, the medication won’t be as effective as it should be. This means that a person taking two doses a day can’t miss more than 3 doses a month.

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