Amprenavir (Agenerase) is one of the class of anti-HIV drugs called protease inhibitors. These drugs work by blocking a part of HIV called protease. When protease is blocked, HIV makes copies of itself that can't infect new cells. Agenerase is now approved for prescription. Agenerase is the fifth protease inhibitor to be approved for the treatment of HIV infection.

Taking the drug: The standard dose of Agenerase is 1,200mg (8 pills) taken twice-a-day with or without food.

Trial results: One study compared the triple combination of Agenerase, AZT (Retrovir) and 3TC (Epivir) to the double combination of AZT/3TC. This study started some time ago. The double combination of AZT/3TC is no longer recommended for the treatment of HIV. No-one in this study had taken anti-HIV drugs before. The study only lasted six months. At the end of the study, just over half of the 116 people taking Agenerase/AZT/3TC had viral loads less than 400 copies. In the AZT/3TC group, only 11% ( 1 in 10) of people had viral loads less than 400 copies. The average; increase in T-cell counts was about the same in both groups.

Another study compared Agenerase taken with two NRTIs (the approved NRTI drugs are: AZT, ddI, ddC, d4T, 3TC and abacavir) to the combination of Crixivan (indinavir) with two NRTIs. People in this study were allowed to have taken NRTI anti-HIV drugs in the past. This study has only been going on for six months. So far, 109 of the 254 people (43%) in the Agenerase/AZT/3TC group have viral loads less than 400 copies. In the Crixivan/AZT/3TC group 132 of the 250 people (53%) have viral loads less than 400 copies.

Side effects: The major side effects of Agenerase are nausea, vomiting, diarrhea, headache, stomach pains/gas, rash and numbing sensations on the skin, particularly around the mouth. It's important to know that Agenerase contains a substance called sulfa that some people are allergic to. A much better known sulfa drug is the anti-PCP drug Bactrim/Septra, and it is well known that some people can't take Bactrim due to an allergic reaction that usually causes a severe skin rash. In studies, about 1 in 4 people taking Agenerase have developed skin rashes. In some cases the rash is mild and treatment can be continued. About 1 in 100 (1%) of people taking Agenerase developed a severe, life-threatening allergic reaction called Stevens-Johnson Syndrome (SJS). In cases of severe rash, Agenerase must be stopped. In studies, about 1 in 3 (around 30%) of people taking Agenerase chose to drop out and stop taking the drug. About half of these drop-outs were due to side effects.

So far, Agenerase does not seem to be causing increased fat levels in the blood, a known side effect of the approved protease inhibitors. But Agenerase studies may not have been going on long enough for this side effect to show up. People taking Agenerase should still have fat levels called triglycerides and cholesterol monitored regularly. Protease inhibitors have also been associated with high blood sugar and diabetes, and these side effects should be watched for if you're taking Agenerase.

Combining Agenerase with other anti-HIV drugs: There are no serious interactions between amprenavir and nucleoside analog anti-HIV drugs (AZT, ddI, ddC, d4T, 3TC, abacavir). An early study found that amprenavir can be safely used in double-protease inhibitor combinations. The following combinations have been studied in a small number of people: Agenerase/indinavir (Crixivan), Agenerase/nelfinavir (Viracept) and Agenerase/saquinavir (Fortovase). No changes in doses were needed. Ritonavir (Norvir) significantly boosts Agenerase levels in the body and the best doses for this combination are not yet certain.

The NNRTI drugs delavirdine (Rescriptor) and nevirapine (Viramune) have not been studied with Agenerase. Based on what is already known about the drugs, it is likely that Rescriptor will increase Agenerase levels. Viramune is likely to reduce Agenerase levels. A study has shown that efavirenz (Sustiva) lowers Agenerase levels in the body. It is recommended that people taking Sustiva and Agenerase together either increase the Agenerase dose to 1,200 mg three times a day or take 100mg of ritonavir (Norvir) along with 1,200mg of Agenerase twice a day.

Vitamin E warning: Each Agenerase pill contains 109 IU of vitamin E per capsule. This means that if you're taking Agenerase, you're also taking 1,744 IU of vitamin E per day. Because vitamin E can thin the blood, you should not take any other vitamin E supplements in addition to Agenerase. People taking blood-thinning drugs should talk to their doctor about the amount of vitamin E in Agenerase to make sure it isn't dangerous to your health.

Drug interactions: The drugs astemizole (Hismanal), cisapride (Propulsid), triazolam (Halcion), midazolam (Versed) and drugs called ergot derivatives should not be taken with Agenerase as the interactions can be life-threatening. The TB drug rifampin should not be taken with Agenerase as it lowers the amount of amprenavir in the body. If rifabutin must be taken with Agenerase, the dose of rifabutin should be cut in half.

The manufacturer of Agenerase has set up a patient assistance program for people having trouble accessing or affording the drug. Call (800) 722-9294 for more information.