AIDS Committee of Windsor: HIV Treatment Information

Summary:
ddC is a type of anti-HIV drug called a "nucleoside analogue reverse transcriptase inhibitor." The most common side effect of ddC is peripheral neuropathy. Other side effects include headache, oral ulcers, fatigue, nausea, abdominal pain, and diarrhea. ddC is taken 3 times daily.

What is it?
ddC, also known as zalcitabine and sold under the brand name Hivid, is a nucleoside analogue reverse transcriptase inhibitor, a type of antiretroviral drug. Antiretroviral drugs fight HIV infection by interfering with the life cycle of the virus. At each stage of this cycle, chemicals called enzymes help the virus make copies of itself (replicate). Some drugs can inhibit (slow down or stop) the actions of these enzymes. When these enzymes can't perform effectively, the virus does not replicate as efficiently and this slows the progression of HIV disease.

How does ddC work?
HIV infects cells and then replicates with the help of its own enzymes. In the first stage of replication, the enzyme reverse transcriptase converts the genetic material of the virus (RNA) to match the genetic material of the cell (DNA). Nucleoside analogue reverse transcriptase inhibitors (NRTIs or "nukes") like ddC block the building of viral DNA and may also interfere directly with the action of the reverse transcriptase enzyme, preventing it from working properly.

Combination therapy
For many people combination therapy with 3 or more anti-HIV drugs can improve CD4+ counts and viral load measures, and reduce opportunistic infections. Currently, the most popular combinations include 2 NRTIs and 1 protease inhibitor. Using NRTIs with protease inhibitors interferes with the viral life cycle at 2 different stages.

Although there is no "best" combination, it may help to consider the following points when designing an antiretroviral "cocktail".

Combinations to avoid:

AZT + d4T or 3TC + ddC. Before they can go to work against HIV, all nucleoside analogue drugs must be broken down by enzymes inside cells. Because AZT and d4T, or 3TC and ddC need the same cellular enzyme to become active, they compete for the use of that enzyme. As a result of this competition, there may not be enough drug activated to fight HIV.
ddC + ddI or ddC + d4T. Using these drugs together may increase the risk of developing peripheral neuropathy.

Ingredients to consider:

3TC, AZT, d4T, and abacavir can enter the brain. Keeping at least one of these drugs in the cocktail may help prevent the development of dementia or other neurological conditions.

Side effects
The most common side effect of ddC is peripheral neuropathy (tingling, burning, or numbness, usually in the toes), reported by 17-31% of volunteers enrolled in clinical trials. Peripheral neuropathy is often a "dose-related" side effect which may go away when ddC is stopped, although it may take weeks or months for the neuropathy to improve.

Other common side effects reported in trials were headache, oral ulcers, fatigue, nausea, abdominal pain, diarrhea, vomiting, rash, itching, muscular pain, and fever.

The most serious side effect of ddC is pancreatitis, an inflammation of the pancreas, that occurred in less than 1% of trial volunteers. Symptoms of pancreatitis include severe nausea, vomiting, and abdominal pain.

Although there have been no reports of side effects unique to women, Richard Moore and colleagues reviewed the charts of 1,450 HIV-positive people and found that women reported fewer side effects with ddC than did men, although the difference was not statistically significant.

Drug interactions:
Combining ddC with other drugs that can cause either peripheral neuropathy (for example ddI, d4T, or some anti-cancer drugs) or pancreatitis (alcohol, IV pentamidine) may increase the risk of developing those side effects.

Dosage
The recommended dose of ddC is 0.75 mg taken 3 times a day, preferably without food.

Where to get it
ddC is available with a prescription. It is covered by all provincial drug formularies.

This information was provided by the Community AIDS Treatment Information Exchange (CATIE). For more information, contact CATIE at 1-800-263-1638.