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Anti-HIV Drugs
Non-protease drugs gain ground.
Amid fanfare, the first potent non-protease anti-HIV drug, Sustiva (efavirenz), was added in December to the federal "A" list of recommended first-line therapies for HIV (see "Uncle Sam Says"). Sustiva was approved by the Food and Drug Administration last September, based on early clinical trials showing it was as effective as protease inhibitors in stopping HIV. Doctors have welcomed Sustiva as a much-needed alternative, given reports of side effects linked to longterm protease use.
Unfortunately the good news has been tempered by community outrage over the high cost of anti-HIV drugs like Sustiva (see "The Other War On Drugs")
As of December, 17 anti-HIV drugs were being used in thousands of different combination regimens, including two drugs available through expanded-access programs (indicated with an asterisk* below). There's also much excitement about T-20, a potent new "fusion inhibitor" with a unique viral target (See "T-20: The Next Big Gun?"). In an early phase I/II study of T-20, high doses of the drug reduced the level of HIV in patients' blood by 99 percent. Meanwhile, positive reports continue to trickle in about hydroxyurea (Bristol-Myers Squibb), an anticancer drug that works well with ddI and appears to be active against latent HIV.
Following quickly on Sustiva's heels is Ziagen, Glaxo Wellcome's new nucleoside analog drug, which was approved by the FDA in December. Next in line appears to be a Glaxo Wellcome protease inhibitor, Agenerase (amprenavir), formerly known as 141W94. It is available through expanded access for people who have taken at least one protease inhibitor in the past. After that comes Abbott's protease inhibitor, ABT-378. Other promising agents include zinc finger and integrase inhibitors, and compounds that block HIV from binding to immune cells called chemokines or co-receptor blockers.
Meanwhile, side effects and drug toxicities present a serious challenge to long-term use. Clinical trials of Agenerase are testing the drug's effect on lipid metabolism and lipodystrophy, a fat disorder linked mainly to protease inhibitor use. There are other toxicities to watch for: Gilead's Preveon can cause kidney problems linked to an accumulation of the drug in the blood.
The selective table below is designed to note the main features of each drug. Remember: HIV can develop resistance to all HIV drugs, so it's important to choose your initial regimen carefully. Ask your doctor about treatment updates.
| Nucleoside analog reverse transcriptase inhibitors are potent in combination with other drugs; used alone, they lead to HIV resistance. AZT, d4T, 3TC, and abacavir penetrate the blood-brain barrier. Common side effect: lactic acidosis. |
| Drug/Dosage | Side Effects | Drug Interactions | Recommendations |
Retrovir (AZT/ zidovudine)
Glaxo Wellcome
Dose: 300-600 mg/day
Approved for pediatric use. | Nausea, vomiting, anemia, low white-blood-cell counts, bone-marrow damage, headaches, rash, itching, weakness, loss of appetite, muscle loss. | Serious: d4T, toxic bone-marrow drugs (e.g. ganciclovir, chemotherapies, antineoplastics). Possible: Methadone, Dilantin, fluconazole (Diflucan), Depakene, ongoing use of Tylenol, dapsone, pentamidine, probenecid, fencytosine, alpha-interferon, Biaxin, rifabutin, rifampin, ribavirin. | Best on empty stomach; take AZT with food if you have stomach irritation. Take vitamin E, erythropoieitin alpha (EPO), or G-CSF to prevent possible blood-cell damage; B vitamins and manganese. Warning: A structural flaw in AZT may lead to HIV resistance. |
| Combivir (3TC 150 mg/AZT 300 mg) | See 3TC and AZT. | 3TC/AZT combo can cause severe anemia. | Watch for anemia. |
Epivir (3TC, lamivudine)
Glaxo Wellcome
300 mg/day (Two 150 mg/day)
Liquid solution for pediatric use. | Headache, nausea, fatigue, low white-blood-cell count, rare hair loss, neuropathy. | Serious: ddC.
Possible: Bactrim may increase 3TC levels. | Watch for anemia and neutropenia. Monitor triglycerides for pancreatitis, especially in children. Take with or without food. |
Videx (ddI/didanosine)
Bristol-Myers Squibb 400 mg/day
Approved for pediatric use. | Stomach pain, diarrhea, pancreatitis, hepatitis, seizures, headaches; neuropathy with high doses. | Serious: pentamidine, ethambutol. Possible: antineoplastics, alcohol, ganciclovir,ciprofloxacin, cimetidine (Tagamet). Coated pill causes poor absorption of Crixivan, Nizoral (ketoconazole), dapsone, tetracycline (all should be taken two hours apart from ddI.) | Avoid alcohol, which increases risk of pancreatitis. Take on empty stomach at least 30 minutes before meal. |
Hivid (ddC/zalcitabine)
Hoffmann-La Roche
Three 0.75 mg doses/day
Approved for pediatric use. | Skin rashes, canker sores, inflammation of mouth, nausea, neuropathy, upset stomach, pancreatitis, liver damage. | Serious: pentamidine, ddI, 3TC. Avoid other neuropathy-causing drugs (chloramphenicol, Antabuse, dapsone, isoniazid). Possible: Radiation therapy, amphotericin B, pyrimethamine, sulfadiazine, intravenous TMP/SMX (Bactrim), ganciclovir, acyclovir, foscarnet, probenecid. | Watch for neuropathy and pancreatitis. Avoid taking with food if possible. |
Zerit (d4T/stavudine)
Bristol-Myers Squibb
Two 40-mg doses/day
Liquid solution for pediatric use. | Neuropathy, pancreatitis, insomnia, hyperactivity; elevated liver enzymes and anemia at high doses. | Serious: AZT. Possible: Ganciclovir, pentamidine, other drugs that cause neuropathy. | Watch for neuropathy and pancreatitis. Take with or without food. |
* Ziagen (abacavir, 1592U89)
Glaxo Wellcome
300 mg twice a day
Under study for pediatric use. | Headache, fatigue; rare allergy (fever, rash, nausea,dizziness, vomiting); abdominal pain, GI and liver problems. Warning: Stop drug immediately and don't try again if any sign of allergy. | Alcohol increases blood level of Ziagen. | Expanded access for patients failing standard regimens. Compassionate use: adults with HIV dementia and pediatric HIV. Crosses blood-brain barrier. |
| Non-nucleoside analog reverse transcriptase inhibitors (NNRTIs, or non-nukes) may interact with other cytochrome p450-processed drugs: protease inhibitors, oral contraceptives, etc. NNRTIs have a mixed ability to penetrate the blood-brain barrier. Common side effect: mild rash. Some doctors build up drug doses slowly to avoid rash; others worry that dose building increases risk of drug resistance. |
| Drug/Dosage | Side Effects | Drug Interactions | Recommendations |
Viramune (nevirapine)
Roxane Laboratories.
One 200-mg/day dose for 14 days then two 200-mg doses/day.
Expanded access for pediatric use. | Fever, muscle soreness, elevated liver function, rash (possibly indicating life-threatening Stevens-Johnson syndrome in rare cases). | Possible: rifampin, rifabutin, oral contraceptives, protease inhibitors, triazolam and midazolam. Use with fluconazole increases risk of rash. | If rash develops, call your doctor; Benadryl or topical corticosteroids may relieve rash symptoms. Drug crosses the placenta. Take with or without food. |
Rescriptor (delavirdine)
Pharmacia & Upjohn.
400 mg three times a day.
Under study for pediatric use. | Rash (possibly indicating life-threatening Stevens-Johnson syndrome in rare cases). | Serious: terfenadine, astemizole, alprazolam, midazolam, cisapride, rifabutin, rifampin, triazolam, ergot derivatives, amphetamines, nifedipine, anticonvulsants. Possible: Rescriptor increases levels of Biaxin, dapsone, quinidine, warfarin, Crixivan, Fortovase. Take an hour apart from ddI and antacids (Tagamet). | Take with or without food. Take with cranberry or orange juice if you have low stomach acid. If rash develops, call your doctor; Benadryl or topical corticosteroids may relieve rash symptoms. One study shows women may have higher blood levels of Rescriptor. |
*Sustiva (efavirenz, DMP-266)
DuPont Merck. 600 mg once a day.
Approved for pediatric use. | Light-headedness, dizziness, body ache, rash, diarrhea, nausea, flu-like symptoms. | Serious: Fortovase; rifampin (until dosing is clarified). Potential: Drug may slightly increase Novir levels and decrease levels of Crixivan and Angenerase. Sustiva can cause a false positive THC (marijuana) reading on the CediaDau urine test. | Take before bedtime to avoid light-headedness; split dosage between a.m. and p.m. if sleeplessness is a problem. Warning: Not for use in early pregnancy (caused birth defects in some newborn monkeys). Take with or without food. |
| Nucleotide analog reverse transcriptase inhibitors appear potent against HIV. Unknown penetration of blood-brain barrier. |
| Drug/Dosage | Side Effects | Drug Interactions | Recommendations |
* Preveon (adefovir dipivoxil, bis-POM PMEA)
Gilead.
120 mg/day. Dose reduction to 60 mg/day recommended after 16-20 weeks. | Kidney toxicity, nausea, diarrhea, elevated liver enzymes. Preveon depletes the body of a natural substance called L-carnitine. | Serious: drugs toxic to kidney (e.g. foscarnet.) Potential: Positive interaction with 3TC. | Expanded access for those failing standard regimens. Monitor serum creatinine levels; check liver function; take with L-carnitine supplement. Good against herpes viruses. Take with or without food. |
| Protease inhibitors (PIs) are very potent and may interact with other drugs using cytochrome p450 metabolic pathways. Potentially life-threatening if taken with Seldane, Hismanal, Propulsid, Halcion, or Versed. Avoid rifabutin, Nizoral, rifampin. Poor absorption may affect potency. Common side effects: liver toxicity, hypoglycemia, flatulence, bloating, lipodystrophy (fat distribution). Monitor liver and glucose levels. |
| Drug/Dosage | Side Effects | Drug Interactions | Recommendations |
Fortovase (saquinavir)
Hoffmann-La Roche
1,200 mg three times a day. 400-800 mg twice a day with Norvir)
Invirase: old formula.
Under study for pediatric use. | Diarrhea, gas, nausea, stomach cramps, heartburn, fatigue, numbness, rash; elevated liver enzymes. | Serious: In early studies, Sustiva reduces Fortovase. Possible: phenobarbital, phenytoin, dexamethasone, carbamezapine, Norvir, Viramune. | Take with food or within two hours of eating. Fortovase is more potent than Invirase. Invirase not recommended as first-line therapy due to poor absorption and resistance issues. |
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Norvir (ritonavir)
Abbott Laboratories.
Six 100 mg. twice a day (400-mg doses twice a day with Fortovase). Currently available in liquid forula only (400 mg = 1 tsp.). Liquid solution for children. | Nausea, vomiting, weakness, diarrhea, rash, fatigue, numbness around mouth, changed taste in mouth, elevated liver enzymes. | Serious: A long list. Read package insert carefully. Poor interaction with common antihistamines and antidepressants like Prozac. | Build up to optimal dose over a few days. Take with a full, high-protein meal. Yogurt may reduce side effects. See "Norvir Alert" for tips on taking liquid formulation. |
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Crixivan (indinavir)
Merck & Company.
Three 800-mg doses/day.
Under study for pediatric use. | Kidney stones, anemia, rarely elevates liver enzymes. | Serious: grapefruit juice. Potential: Viramune, Fortovase (poor interaction in test-tube studies), ergot derivatives. | Take on empty stomach with water one hour before or two hours after eating. Drink at least six glasses of water daily to avoid kidney stones. Alternative liquids: juice, skim milk, coffee, tea. Eat with fat free snacks. |
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Viracept (nelfinavir)
Agouron Pharmaceuticals
Three 750 mg doses/day.
Approved for pediatric use: dose 20-30 mg/kg. | Fatigue, rash, nausea, stomach cramps, diarrhea, elevated liver enzymes. | Potential: Increases Fortovase (under study as combo) and Crixivan in preliminary studies. | Take with food. Use Imodium, Lomotil to control diarrhea. Women should consult with their doctors prior to use. Monitor glucose levels to avoid risk of diabetes. |
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*Angenerase (amprenavir/141W94)
Glaxo Wellcome | Nausea, heacache, neuropathy, rash, diarrhea, fatigue. | Possible: Sustiva | Expanded access for patients who have taken at least one other protease inhibitor. Can be taken with or without food. Under study for pediatric use. |
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| Drug/Dosage | Side Effects | Drug Interactions | Recommendations |
Hydrea (Hydroxyurea/HO)
Bristol-Myers Squibb.
Two 500-mg doses/day.
A chemotherapy drug;
probably penetrates blood-
brain barrier.
Available for
pediatric use. | Mild nausea, bone-marrow suppression, hair loss, rare dry mouth. Reduces CD8+ cell activation. | Increases efficacy of ddI, even against ddI-resistant HIV. In vitro synergy with AZT, but risk of bone-marrow suppression. | Animal studies suggest possible toxicity for pregnant women. Monitor bone-marrow suppression, liver and kidney function. Drug attacks a cell enzyme (ribonucleotide reductase); may work against proviral HIV in resting T-cells and macrophages (latent infection). |
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