Standard Treatments for HIV, Spring 1997

This is a brief guide to the antiretroviral drugs approved by the FDA to treat HIV infection.

The current model of care is to use these drugs in combinations that keep both viral replication and drug toxicities as low as possible. HIV can easily develop resistance to any antiretroviral used alone, and so combination therapy has become the standard. However, the best combination, or sequence of combinations, has not been found, and may be different for each person. In making treatment decisions, the following should be considered:

1. Adherence to the prescribed dosing schedule will help prevent treatment failures.

2. There is a growing consensus that whenever antiretroviral treatment is used, the goal should be to keep the viral load so low that it is undetectable.

3. Any change in a combination should involve at least two drugs, since switching or adding just one can make it easy for the virus to become resistant.

4. New Federal guidelines on antiretroviral therapy, representing a consensus of medical experts, are scheduled to be released shortly, and should be consulted.

The side effects described below for each drug may be the most common or important ones, but everyone should be prepared for other possible problems, which are noted at length in the product insert available at pharmacies.

Reverse Transcriptase Inhibitors

These drugs work by inhibiting an enzyme -- reverse transcriptase -- which the virus needs to take over a cell's genetic machinery. The first five agents in this class are also called nucleoside analogs.

* AZT, also called zidovudine, is marketed under the brand name Retrovir(R), and can be combined with most other antiretrovirals. AZT is valuable for treating cognitive problems caused by HIV because it penetrates the central nervous system better than most of the other drugs. It can cause headaches and stomach upset, but these often 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. The dose used for treating cognitive/motor slowing or dementia is twice the regular dose: 1200 mg a day.

* ddI, also known as didanosine, is sold under the brand name VIDEX(R), and can be combined with any other antiretroviral. However, ddI, ddC, and d4T can each cause pancreatitis and peripheral neuropathy, so any combination of these drugs must be carefully monitored. If you experience abdominal pain, or tingling and numbness in your toes or fingers, call your healthcare provider immediately; otherwise, long-term damage may result. 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.

* ddC, also called zalcitabine, is sold as HIVID(R), and can be combined with any other antiretroviral. However, ddC, ddI, and d4T can each cause pancreatitis and peripheral neuropathy, so any combination of these drugs must be carefully monitored. If you experience abdominal pain or tingling and numbness in your toes or fingers, call your provider immediately; otherwise, long-term damage may result. The usual prescription for ddC is one tablet (0.75 mg) taken three times a day.

* d4T, also known as stavudine, is marketed as ZERIT(R), and can be combined with most other antiretrovirals. However, d4T, ddI, and ddC can each cause pancreatitis and peripheral neuropathy, so any combination of these drugs must be carefully monitored. If you experience abdominal pain or tingling and numbness in your toes or fingers, call your provider immediately; otherwise, long-term damage may result. The usual prescription for d4T is one capsule (20, 30 or 40 mg, depending on body weight) taken twice a day.

* 3TC, also called lamivudine, is marketed as Epivir(R). 3TC can be combined with any other antiretroviral and may resensitize HIV to AZT in people whose virus has become resistant to that drug. 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.

Non-Nucleoside Reverse Transcriptase Inhibitors

* Nevirapine is sold under the brand name Viramune(R). It has been combined with all other antiretrovirals. Nevirapine can cause a serious rash, but this may 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 antiretrovirals, so ask your provider about dose adjustments for those drugs.

* Delavirdine (brand name Rescriptor(R)) has been used with all other antiretrovirals. Like 3TC, delavirdine may resensitize the virus to AZT in people who have become resistant. And 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.

Protease Inhibitors

These drugs target a different enzyme of the virus -- protease -- which is essential for HIV to make working copies of itself. More than with most drugs, it is very important not to miss doses of the protease inhibitors, since HIV can develop resistance if drug levels in the body become too low.

* Nelfinavir is approved under the trade name VIRACEPT(R). It has been combined with all of the nucleoside analogs, but its use with the other drugs is not well documented. It is potent, easy to tolerate, and virus which grows resistant to it might not be resistant to the other protease inhibitors. It can cause stomach upset or headaches in some people, 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. Try not to miss any doses of this drug, or the virus could become resistant.

* Saquinavir is sold under the brand name Invirase(TM). It can be combined with most other antiretrovirals, and may work especially well with ritonavir, using the low doses tested in clinical trials. Saquinavir can cause mild 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 three capsules (600 mg) taken three times a day with food. The current formulation of saquinavir is very poorly absorbed, but taking it with grapefruit juice helps to increase blood concentrations. A better formulation will probably be available this year. Try not to miss any doses of this drug, or the virus may become resistant.

* Ritonavir is marketed as Norvir(R). Ritonavir can be combined with most other antiretrovirals, but should not be used with indinavir. However, ritonavir may work especially well in combination with saquinavir, using the low doses tested in clinical studies. There are many medications that should be taken with caution or not at all with ritonavir, so tell your provider exactly what other drugs you are on, prescribed or otherwise. Ritonavir can cause stomach upset, generalized discomfort and tingling or numbness around the mouth. These might by 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 if combined with saquinavir. The capsules should be stored in a refrigerator. Try not to miss any doses of this drug; the virus may become resistant.

* Indinavir is sold under the brand name Crixivan(R). Indinavir can be used with most other antiretrovirals, but should not be combined with ritonavir. 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. Try not to miss any doses of this drug, or the virus could become resistant.

Miscellaneous

* Hydroxyurea is marketed as Hydrea(R) and is used to treat a number of different cancers. While it is not widely considered a standard anti-HIV drug, and not FDA approved for this purpose, we include it because it has been shown in research to inhibit a human enzyme -- ribonucleotide reductase -- which the virus needs. Like AZT, hydroxyurea can cause anemia and neutropenia, although this is unlikely using the low dose usually prescribed for HIV: one capsule (500 mg) once or twice a day.