Antiviral Therapy

IS THE HIV LIFE CYCLE?

There are several steps in the HIV

life cycle. See Fact Sheet 415

for a diagram.

1. Free virus circulates in the bloodstream.

2. HIV attaches to a cell.

3. HIV empties its contents into the cell (infects the cell).

4. The HIV genetic code (RNA) is changed into DNA by the reverse

transcriptase enzyme.

5. The HIV DNA is built into the infected cell’s DNA by the integrase

enzyme.

6. When the infected cell reproduces, it activates the HIV DNA,

which makes the raw material for new HIV viruses.

7. Packets of material for a new virus come together.

8. The immature virus pushes out of the infected cell in a process

called “budding.”

9. The immature virus breaks free of the infected cell.

10. The new virus matures: raw materials are cut by the protease

enzyme and assembled into a functioning virus.

WHAT ARE THE

ANTIVIRAL DRUGS?

Each type, or “class”, of antiviral drugs attacks

HIV in a different way. The first class of anti-HIV drugs was

the nucleoside reverse transcriptase inhibitors, also called “nukes”.

These drugs work by blocking Step 4, where the HIV genetic material

is converted from RNA into DNA. Approved drugs in this class include:

• AZT (ZDV, zidovudine, Retrovir®)
• ddI (didanosine, Videx®)
• ddC (zalcitabine, Hivid®)
• d4T (stavudine, Zerit®)
• 3TC (lamivudine, Epivir®)
• Abacavir (Ziagen®)
• Tenofovir (Viread®)
• Combivir® (AZT/3TC combination)
• Trizivir® (AZT/3TC/Abacavir

  combination)

Another class of drugs blocks the same step of the life cycle,

but in a different way. This class is the non-nucleoside reverse

transcriptase inhibitors, or NNRTIs. Three NNRTIs have been approved:

• Nevirapine (NVP, Viramune®)
• Delavirdine (DLV, Rescriptor®)
• Efavirenz (EFV, Sustiva®)

There has been a lot of excitement about the third class of

antiviral drugs, the protease inhibitors. These drugs block Step

7, where the raw material for new HIV virus is cut into specific

pieces. Five protease inhibitors have been approved:

• Saquinavir (SQV, Invirase®

  and Fortovase®)

• Indinavir (IDV, Crixivan®)
• Ritonavir (RTV, Norvir®)
• Nelfinavir (NFV, Viracept®)
• Amprenavir (APV, Agenerase®)
• Lopinavir (LPV, Kaletra®)

HOW ARE THE DRUGS

USED?

When HIV multiplies, most of the new copies are mutations:

they are slightly different from the original virus. Some mutations

keep multiplying even when you are taking an antiviral drug. When

this happens, the drug will stop working. This is called “developing

resistance” to the drug.

If only one antiviral drug is used, it is easy for the virus

to develop resistance. But if two drugs are used, a successful

mutant would have to “get around” both drugs at the

same time. And if three drugs are used, especially if they attack

HIV at different points in its life cycle, it’s very hard for

a mutation to show up that can resist all three drugs at the same

time.

Using a triple-drug combination means that it takes much longer

for resistance to develop. For this reason, using just one antiviral

drug (monotherapy) is not recommended.

CAN THESE DRUGS

CURE AIDS?

A blood test called the “viral

load” measures the amount of HIV virus in your bloodstream.

People with lower viral loads stay healthier longer. See Fact

Sheet 413 for more information on the viral load test.

Some people’s viral load is so low that it is “undetectable”

by the viral load test. This does not mean that all the

virus is gone. Researchers used to believe that antiviral therapy

could eventually kill off all of the HIV virus in the body. Now

this seems unlikely.

WHEN DO I START?

There is not a clear answer to this question. Most doctors

will consider three things: 1) your viral

load; 2) your T-cell count;

and 3) any symptoms you’ve had. Antiviral therapy is usually started

if your viral load is over 30,000, if your T-cell count is below

350, or if you’ve had any symptoms of HIV disease. This is an

important decision you should discuss with your doctor.

WHICH DRUGS DO

I USE?

Each antiviral drug has side effects. Some are serious. Refer

to the fact sheet for each individual drug. Some combinations

of drugs are easier to tolerate than others, and some seem to

work better than others. Each person is different, and you and

your doctor will have to decide which drugs to use.

The viral load test is now being used to see if antiviral drugs

are working. If the viral load does not go down, or if it goes

down but comes back up, it might be time to change antiviral drugs.

 WHAT’S

NEXT?

New drugs are being developed in all three of the existing

classes. Researchers are also trying to develop new types of drugs,

such as drugs that will block HIV from attaching to cells (Step

2), and drugs that will strengthen the body’s immune defenses.

Revised January 9, 2002

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