HIV Treatment Options

This is AIDS Treatment News' third annual overview of antiretroviral drugs.

The best use of these drugs is still evolving, but several ideas have become the foundation for the current standard of care:

1. The goal of effective treatment is to slow viral replication to undetectable limits. Today that usually requires at least three drugs.

2. Resistance to these drugs can develop quickly if too many doses are missed. So if a drug is too difficult to tolerate or too complicated to manage, it should be replaced with another choice.

3. Viral loads that rise appreciably above detectable limits suggest that resistance to one or more of the drugs has developed, and a change of treatment should be considered. As with CD4 counts, one lab result is not a dependable trigger for a major decision; at least one more viral load should be drawn. But once a decision is made to change a regimen, all three drugs should be replaced at the same time, since switching or adding just one or two makes it easy for the virus to become resistant again.

Common adult doses are given for the drugs listed below; pediatric dosing and formulations can be found in the Physician's Desk Reference. Also, the side effects described are only the most common or important ones, and everyone should be prepared for less expected effects. If you are having a problem with your medications, or stop taking them for any reason, call your health-care provider immediately.


Nucleoside Analog Reverse Transcriptase Inhibitors

These drugs work by inhibiting an enzyme--reverse transcriptase--which the virus needs to take over a cell's machinery.

AZT, also called zidovudine, is marketed under the brand name Retrovir®. AZT can be combined with most other antiretrovirals, but probably should not be used with d4T. It can cause headaches and stomach upset, but these usually go away after a couple weeks. Over extended periods of use, it can cause anemia (low production of red blood cells), neutropenia (low white cells) and myopathy (damage to muscle fibers). These problems resolve if the drug is discontinued. The usual prescription for AZT is two capsules (200 mg) taken three times a day, or one 300 mg capsule taken twice a day. AZT is also marketed in a tablet called Combivir, which also contains 3TC (300 mg of AZT and 150 mg of 3TC). There is a liquid suspension as well, which is easier to manage for children and people who have difficulty swallowing.

ddI, or didanosine, is sold under the brand name VIDEX® and can be combined with most other antiretrovirals. It can cause pancreatitis and peripheral neuropathy, so if you experience abdominal pain, or tingling and numbness in your toes or fingers, call your provider. The usual prescription for ddI is two tablets (125 or 200 mg, depending on body weight) taken twice a day on an empty stomach with water. Many people do not like the chalky texture of the original ddI formulation; the orange-flavored version may be a bit easier to take. It also comes in a powder that can be mixed in water. Some providers feel that ddI is just as effective and more convenient if the entire daily amount is taken in one dose. But in that case, the strength and number of tablets must be calibrated to obtain the correct level of buffering agent in the tablets. A pharmacist can figure that out.

ddC, or zalcitabine, is sold as HIVID®, and can be combined with most other antiretrovirals. Like ddI, ddC can cause pancreatitis and peripheral neuropathy; if you experience abdominal pain or tingling and numbness in your toes or fingers, call your provider. The usual prescription for ddC is one tablet (0.75 mg) taken three times a day.

d4T, or stavudine, is marketed as Zerit®. It can be combined with most other antiretrovirals, but probably should not be used with AZT. Like the other "d" drugs, d4T can cause pancreatitis and peripheral neuropathy, so if you experience abdominal pain, or tingling and numbness in your toes or fingers, call your provider. The usual prescription for d4T is one capsule (30 or 40 mg, depending on body weight) taken twice a day. It also comes in a liquid suspension.

3TC, or lamivudine, is marketed as Epivir®, and can be combined with any other antiretroviral. It can cause headaches and insomnia in some people, but these usually go away after a few weeks. The usual prescription for 3TC is one tablet (150 mg) taken twice a day. It also comes in a tablet called Combivir that has AZT added (300 mg of AZT and 150 mg of 3TC). And it comes in a liquid suspension as well.

Abacavir, also known as 1592 or Ziagen(tm), is dispensed through an "expanded-access" program, which means it is still experimental but is available for persons who have failed other therapies. Abacavir is an important drug, but users need to know about a potentially serious hypersensitivity reaction that happens in about 3% of patients; this usually begins from a few days to four weeks after starting the drug, and it will go away without further problem if the drug is stopped and not restarted. If you develop fever, nausea, and malaise (and sometimes a rash) while taking this drug--signs of this reaction--call your provider immediately. If you stop taking abacavir because of hypersensitivity, NEVER RESTART IT, since restarting after hypersensitivity can cause a more serious and possibly fatal reaction. Dosing for abacavir is 300 mg taken twice a day.


Non-Nucleoside
Reverse Transcriptase Inhibitors

Nevirapine is sold under the brand name Viramune®, and has been combined with all other antiretrovirals. Nevirapine can cause a serious rash, but this can usually be avoided by starting with a low dose, one tablet taken once a day for two weeks, and then doubled to the usual prescription: one tablet (200 mg) twice a day. Nevirapine may lower the blood levels of other drugs; when combined with indinavir in particular, the indinavir is usually increased from 800 mg to 1000 mg each dose.

Delavirdine is approved as Rescriptor®, and has been used with all other antiretrovirals. Like nevirapine, it can cause a rash in some people. The usual prescription for delavirdine is four pills (400 mg) taken three times a day.

Efavirenz, also known as DMP-266 or SUSTIVA(tm), is available under an expanded-access program to people with CD4 counts of 400 or less and a history of failing the approved antiretrovirals. This drug can cause light-headedness when taken with AZT, 3TC or indinavir; it can also cause kidney irritation, so that drinking plenty of water is important. The usual dosing for efavirenz is three pills (600 mg) taken once a day, although the expanded-access protocol allows for one pill taken three times a day. Efavirenz, like nevirapine, may lower the levels of other drugs. If combined with indinavir, each indinavir dose should be increased from 800 mg to 1000 mg. Efavirenz should NOT be taken during pregnancy, since it was reported to cause birth defects in recent monkey studies.


Nucleotide Reverse
Transcriptase Inhibitors

Adefovir, also known as bis-POM PMEA or PREVEON(tm), is available through an expanded-access program for people who have failed at least two nucleoside analogs and one protease inhibitor. Adefovir can cause nausea and vomiting, and may lower levels of carnitine in the body. Dosing for adefovir is one pill (120 mg) taken once a day with 500 mg of carnitine.

Protease Inhibitors

These drugs target a different enzyme of the virus--protease--which is essential for HIV to assemble working copies of itself.

Saquinavir is sold under the brand name FORTOVASE®. (An older version, called Invirase, was not absorbed very well; note the new dosing for Fortovase.) Saquinavir can be combined with all other antiretrovirals, and may work especially well with ritonavir, using lower doses of both drugs. Saquinavir can cause stomach upset and elevated liver enzymes, and should be used with caution with certain other medications. The usual prescription for saquinavir--unless combined with ritonavir--is six capsules (1200 mg) taken three times a day with food. The usual dose when combined with ritonavir is 400 mg of each drug, taken twice a day.

Ritonavir is marketed as Norvir®. Ritonavir can be combined with most other antiretrovirals, and may work especially well in combination with saquinavir, using a low dose. However, there are many drugs, both prescribed and recreational, that should be taken with caution or not at all with ritonavir. Make your provider aware of all drugs you might take. Ritonavir can cause stomach upset, generalized discomfort and tingling or numbness around the mouth. These might be avoided by starting with a low dose, three capsules taken twice a day with food, and adding one capsule each dose every couple days until the usual prescription is tolerated: six capsules (600 mg) taken twice a day. That dose will be lower, 400 mg, if combined with saquinavir. The capsules should be stored in a refrigerator. There is also a liquid formulation of ritonavir.

Indinavir is sold under the brand name Crixivan®, and can be used with most other antiretrovirals. Indinavir can cause stomach upset, kidney stones and generalized discomfort, although drinking plenty of fluids may prevent the kidney stones. It should be used with caution with certain other medications, so make sure your provider knows about everything you are taking. The usual prescription for indinavir is two capsules (800 mg) taken three times a day on an empty stomach with a large glass of water. That dose may be larger, 1000 mg, if indinavir is combined with nevirapine or efavirenz.

Nelfinavir is approved under the trade name Viracept®, and has been combined with all other antiretrovirals. It can cause stomach upset and diarrhea, and should be used with caution with certain other medications. The usual prescription for nelfinavir is three tablets (750 mg) taken three times a day with food. But it may also be effective when taken twice a day, five tablets (1250 mg) each dose. There is a powdered formulation of nelfinavir that can be mixed in water.


Ribonucleotide Reductase Inhibitors

This class targets an enzyme which the virus needs and which is made by blood cells. So far, the only available drug which works this way is hydroxyurea, which was approved years ago to treat certain cancers. But at least one more drug like this is under development.

Hydroxyurea, also called Hydrea, may work especially well with ddI. It can lower white and red cell counts, although that is unlikely at the low doses used for HIV infection: 500 to 1000 mg daily. (It may be more likely, however, when combined with drugs that pose the same problem, such as AZT or ganciclovir.) The effect of hydroxyurea on HIV replication is somewhat indirect, so it should probably be considered only an addition to a standard, three-drug regimen.