May 19, 2000
In recent years the drug choices available to people with HIV have increased substantially. There are currently 16 approved antiviral drugs for HIV and these drugs are usually used in combinations of three or more to create an effective antiviral therapy. In the next several Ezines we are going to review each of the three classes of drugs currently approved by the Food and Drug Administration (FDA), and each of the 16 drugs within those classes.
The first class of drugs approved by the FDA are NRTIs. NRTIs work by binding to an enzyme in the system called reverse transcriptase and preventing the HIV viral RNA from converting to into double-stranded DNA. By preventing this reverse transcription from occurring, NRTIs successfully interfere with one of the steps of the HIV life-cycle and prevent the virus from being able to reproduce. NRTIs are sometimes referred to as nukes, short for nucleoside.
There are several drugs in the NRTI class that are currently used as part of an effective antiviral combination therapy. Many combinations include two NRTIs plus one or more drugs in another class, and research is being done to study the effectiveness of using three NRTIs as the sole antiviral therapy.
Commonly known as AZT, this was the first FDA-approved HIV antiviral. AZT is usually taken as one 300-mg tablet twice a day. There are no food restrictions with this drug. AZT can create side effects such as headaches, hypertension, and fatigue; however, these side effects will usually diminish or disappear over time. In some people, AZT can cause bone marrow damage leading to anemia (shortage of red blood cells) or granulocytopenia (shortage of white blood cells.)
ddI can cause pancreatitis, a life-threatening inflammation of the pancreas.
Commonly called ddI, this drug is usually taken as two 100-mg tablets every 12 hours. (Please note the distinction between "twice a day" and "every 12 hours.") Once-a-day dosing of ddI was approved in November 1999, and is two 200-mg tablets taken at the same time. (Note: the once-a-day dosing tablets cannot be used for twice-daily dosing. If you want to change how often you take ddI, talk to your primary care provider.) Because it is important that the drug be taken on an empty stomach to maximize absorption, take ddI at least one hour before or two hours after a meal. Avoid alcohol if you are taking ddI. It is important that the drug be taken on an empty stomach to maximize absorption. Side effects noted with ddI are headache, hypertension, nausea, insomnia, diarrhea, and liver failure. This drug may also cause inflammation of the pancreas (pancreatitis) which can be life-threatening if not treated. (Symptoms of pancreatitis include pain in the stomach and back, nausea, vomiting, and blood in the urine.)
Commonly called ddc, this drug is usually taken as one 0.75-mg tablet every 8 hours. Food restrictions are no food at least one hour before or two hours after a meal. Common side effects are headache, hypertension, rash, fever, nausea, and changes in liver function. (Careful kidney and liver monitoring by your physician is needed if you are taking ddc.) More serious side effects include pancreatitis and peripheral neuropathy. Peripheral neuorpathy is a form of nerve damage that causes tingling, numbness, or sharp burning pains in the feet, hands, or legs. If you experience peripheral neuorpathy, tell your doctor! This side effect can go away if the drug is stopped, but can become permanent if nerve damage develops.
Commonly called d4T, this drug is usually taken as one 40-mg capsule twice a day. There are no food restrictions with d4T. Common side effects are headaches, hypertension, and fatigue. Peripheral neuropathy is also a potentially severe side effect of d4T and you should see your doctor if you have any symptoms of peripheral neuropathy. In some cases, lowering the dosage can eliminate the peripheral neuropathy and still provide good viral suppression. Another side effect that d4T is suspected of causing is lipoatrophy, loss of subcutaneous fat from the face, arms, and legs.
Commonly referred to as 3TC, this NRTI is usually taken as one 150-mg tablet twice a day. There are no food restrictions with 3TC. Potential side effects are headache, nausea, fatigue, and peripheral neuropathy.
Commonly referred to as abacavir, this is the newest of the FDA-approved NRTIs. It is taken as one 300-mg tablet twice a day. Common side effects are headache, fatigue, and high blood pressure. A severe, but rare, side effect of abacavir is hypersensitivity. Hypersensitivity reaction to abacavir appears as fever, nausea, and skin rash. Fever is the key side effect. Often the hypersensitivity can be treated until it disappears; contact your doctor if you experience this side effect. Do not stop the drug and try to retake the drug at a later date if you have experienced hypersensitivity! Attempting to retake abacavir after stopping due to hypersensitivity can lead to hospitalization and possibly death.
Combivir is commonly known by its own name. It is a combination of the drugs AZT (300-mg) and 3TC (150-mg) previously mentioned. Combivir is taken as one tablet twice a day, and has no food restrictions. The side effects profile is the same as previously described for AZT and 3TC.
This completes the list of currently approved NRTIs for use in combination therapy for HIV. Detailed fact sheets are available on each of these drugs. E-mail us your full name and mailing address, with the name of the drug you are interested in, to request a copy. E-mail to: email@example.com.
In the next issue, we will cover the class of drugs called Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs).