What is Aptivus?

• Aptivus is an anti-HIV medication. It is in a category of HIV medicines called protease inhibitors (PIs). Aptivus prevents cells infected by HIV from producing new virus. This reduces the amount of virus in your body.
   
• Aptivus must be used in combination with Norvir (ritonavir) and at least two other anti-HIV drugs.
   
• Aptivus, manufactured by Boehringer Ingelheim, was approved for the treatment of HIV by the U.S. Food and Drug Administration (FDA) in June 2005. Aptivus/ritonavir is only approved for HIV-infected people who have tried and failed other anti-HIV drug regimens (including those containing protease inhibitors) in the past. It is not approved for HIV-infected people starting anti-HIV treatment, or a protease inhibitor, for the first time (unless they were infected with a strain of HIV resistant to multiple protease inhibitors).

• Aptivus has a different structure than other protease inhibitors and is active against strains of the virus that are resistant to the other protease inhibitors that are currently available.
   
• The correct dose of Aptivus is 500mg twice a day (two 250mg capsules twice daily) . To help keep levels of Aptivus high in the blood, which is very important for the drug to be effective, it is necessary to combine Aptivus with low doses (200mg twice daily) of the protease inhibitor Norvir (ritonavir).
   
• Aptivus/ritonavir should be taken with food, preferably a complete nutritious meal, to ensure proper absorption of the drug into the bloodstream.
   
• Aptivus is recommended by the U.S. Department of Health and Human Services (DHHS) for HIV-positive people who have tried and failed other protease inhibitors in the past. It is not recommended by the DHHS for patients who are new to anti-HIV treatment or starting a protease inhibitor for the first time.
   
• Clinical trials have demonstrated that Aptivus is an effective option for patients who are not likely to respond to older protease inhibitors, especially when it is combined with other anti-HIV medications that a patient's virus is still at least partially sensitive to.
   
• Aptivus/ritonavir works best when it is combined with anti-HIV drugs that the virus is still sensitive to. However, this can be challenging for HIV-positive people who have tried and failed several anti-HIV drug regimens in the past. Drug resistance tests, such as genotypic assays and phenotypic assays, can be very useful in figuring out which anti-HIV drugs the virus is still likely to respond to. Drug-resistance tests are recommended when putting together a regimen that contains Aptivus/ritonavir. In clinical trials, Aptivus/ritonavir worked best when it was combined with Fuzeon (enfuvirtide; T-20), particularly in people who had not been on Fuzeon in the past.
   
• A clinical trial of Aptivus has been discontinued due to limited effectiveness, along with earlier concerns of liver toxicities, in patients starting treatment for the first time.
  
  Study 1182.33 was designed to evaluate the effectiveness and safety of Aptivus (500 mg twice daily) combined with one of two doses of Norvir (100 or 200 mg twice daily) compared to Kaletra (lopinavir plus ritonavir) in HIV-positive volunteers starting treatment for the first time. In February, the manufacturer announced that it was discontinuing the study's evaluation of Aptivus plus 200 mg Norvir due to higher rates of liver enzyme increases.
  
  While the manufacturer opted to continue studying Aptivus plus 100 mg Norvir, more volunteers taking Aptivus plus lower-dose Norvir had detectable viral loads (above 50 copies/mL) after 60 weeks of treatment, compared to those in the Kaletra group. As a result, the study of Aptivus plus 100 mg Norvir was terminated as well.
  
  These study results suggest that Aptivus will not likely be a recommended protease inhibitor option for HIV-positive people starting therapy for the first time.
   
• Aptivus/ritonavir is not approved for use in HIV-positive children. To learn about treatment options for children, click here.

• Because of the ways Aptivus and ritonavir are metabolized (broken down) in the body, they can interact with many other medications used to treat HIV, AIDS-related complications, and other diseases. Aptivus/ritonavir may cause blood levels of other medications to be become too low (which can decrease their effectiveness) or high (which can increase the risk of side effects). Similarly, other medications may cause blood levels of Aptivus and/or ritonavir to become too low or high.
   
• Tell your doctors and pharmacists about all medicines you take. This includes those you buy over-the-counter and herbal or natural remedies, such as St. John's wort. Bring all your medicines when you see a doctor, or make a list of their names, how much you take, and how often you take them. Your doctor can then tell you if you need to change the dosages of any of your medications.
   
• The following medications should not be taken while you are being treated with Aptivus/ritonavir:
  Antifungals: Vfend (voriconazole)
  Acid reflux/heartburn medications: Propulsid (cisapride)
  Antibiotics: Rifadin (rifampin)
  Antimigraine medications: Methergine, Methylergometrine (methylergonovine); Ergostat, Cafergot, Ercaf, Wigraine (ergotamine); Ergotrate, Methergine (ergonovine); or D.H.E. 45, Migranal (dihydroergotamine)
  Antihistamines: Hismanal (astemizole) or Seldane (terfenadine)
  Heart medications: Cordarone (amiodarone), Vascor (bepridil), Tambocor (flecainide), Rythmol (propafenone), or Quinaglute/Quinidex (quinidine)
  Cholesterol-lowering drugs (statins): Zocor (simvastatin) and Mevacor (lovastatin)
  Antipsychotics: Orap (pimozide)
  Sedatives: Versed (midazolam) and Halcion (triazolam)
  Enlarged prostate: Uroxatral (alfuzosin)
  Herbal products: St. John's wort
   
• Aptivus/ritonavir can greatly decrease the levels of other protease inhibitors—including Agenerase (amprenavir), Lexiva (fosamprenavir), Kaletra (lopinavir), and Invirase (saquinavir)—in the blood. It is currently recommended that Aptivus/ritonavir not be taken with other protease inhibitors, until adequate drug-interaction and dosing studies have been completed. Aptivus/ritonavir can interact with anti-HIV nucleoside reverse transcriptase inhibitors (NRTIs). Aptivus/ritonavir decreases Ziagen (abacavir) levels in the blood by 40% and Retrovir (AZT) levels by 35%. It might be necessary to increase the doses of Ziagen or Retrovir, if they are combined with Aptivus/ritonavir. However, no dosing recommendations have been made. Aptivus/ritonavir can also decrease levels of Videx/Videx EC (didanosine) in the blood. In turn, Aptivus/ritonavir should be taken at least two hours before or two hours after taking Videx/Videx EC.
   
• Aptivus/ritonavir can interact with some medications used to treat thrush (candidiasis) and other fungal infections. Diflucan (fluconazole) can increase Aptivus levels in the blood (total daily dose of Diflucan should not exceed 200mg). Aptivus/ritonavir may increase Sporanox (itraconazole) or Nizoral (ketoconazole) levels in the bloodstream (total daily doses of Sporanox and Nizoral should not exceed 200mg). It is also possible that Aptivus/ritonavir either increases or decreases Vfend (voriconazole) levels in the blood.
   
• Aptivus/ritonavir can interact with some medications used to treat TB, MAC, and other bacterial infections. Aptivus/ritonavir raises Biaxin (clarithromycin) levels in the bloodstream. Similarly, Biaxin raises Aptivus levels in the bloodstream. The dose of Biaxin does not need to be decreased, although this may be necessary in people with altered kidney function. Aptivus/ritonavir can also increase Mycobutin (rifabutin) levels in the bloodstream. If Mycobutin is taken at the same time as Aptivus/ritonavir, it is recommended that the Mycobutin dose be reduced to 150mg every other day.
   
• Aptivus/ritonavir may interact with calcium channel blockers, medications used to treat heart disease. Studies of Aptivus/ritonavir combined with calcium channel blockers have not yet been conducted. Healthcare providers should be cautious when prescribing Aptivus/ritonavir with either Cardizem (diltiazem), Plendil/Lexxel (felodipine), Cardene (nicardipine), Sular (nisoldipine), or Calan/Verelan (verapamil). Aptivus/ritonavir should not be combined with Vascor (bepridil).
   
• Aptivus/ritonavir may increase blood levels of Norpramin (desipramine), a drug used to treat depression. The dose of Norpramin may need to be decreased.
   
• Antabuse (disulfiram) is a medication taken by people with an alcohol-dependency problem. This medication can make people very sick if they consume even small amounts of alcohol. Because Aptivus/ritonavir contains small amounts of alcohol, it should not be combined with Antabuse.
   
• Flagyl (metronidazole) is used to treat some types of parasitic infections. People should not drink alcohol—or take medications that contain alcohol (such as Aptivus/ritonavir)—while taking this drug. The combination of alcohol and Flagyl can cause someone to become very ill. In turn, HIV-positive people taking Aptivus/ritonavir should not take Flagyl.
   
• Cholesterol-lowering drugs, also known as "statins," can interact with Aptivus/ritonavir. There are two statins that should not be used with Aptivus/ritonavir: Zocor (simvastatin) and Mevacor (lovastatin). Levels of these two drugs can become significantly increased in the bloodstream if they are combined with Aptivus/ritonavir, which increases the risk of side effects. The two statins that are believed to be the safest in combination with Aptivus/ritonavir are Pravachol (pravastatin) and Lescol (fluvastatin). It is also possible to take Aptivus/ritonavir with Lipitor (atorvastatin), although Aptivus/ritonavir can increase the levels of this drug in the bloodstream. If Lipitor is prescribed, it's best to begin treatment with the lowest possible dose of the drug and then increase the dose if necessary. Little is known about the newest statin, Crestor (rosuvastatin), in combination with Aptivus/ritonavir.
   
• Demerol (meperidine) is a powerful analgesic (painkiller). Aptivus/ritonavir can decrease meperidine, but can increase the amount of normeperidine (an active byproduct of Demerol), in the bloodstream. In turn, Demerol should be used cautiously if it must be combined with Aptivus/ritonavir.
   
• Another painkiller, methadone, commonly used to treat drug heroin addiction, can interact with Aptivus/ritonavir. Methadone levels in the bloodstream can decrease when combined with Aptivus/ritonavir. Because of this, it might be necessary to increase the dose of methadone.
   
• Aptivus/ritonavir decreases the amount of oral contraceptives (taken by women to help avoid pregnancy) in the bloodstream. This means that there may be a higher risk of becoming pregnant if Aptivus/ritonavir and oral contraceptives are taken at the same time. To reduce the risk of pregnancy, barrier protection (e.g., condoms) should be used.
   
• Viagra (sildenafil), Levitra (vardenafil) and Cialis (tadalafil) levels in the bloodstream may increase when combined with Aptivus/ritonavir. In turn, it is best to use a lower dose of these drugs in order to reduce the risk of side effects.

• The most common short-term side effects noticed in clinical trials involving HIV-positive people taking Aptivus/ritonavir were: nausea, vomiting, diarrhea, stomach pain, tiredness, and headache.
   
• Aptivus/ritonavir may increase the risk of intracranial hemorrhage (ICH)—bleeding in the brain due to ruptured blood vessels in the head—that can lead to stroke or death. Aptivus/ritonavir should be used with caution in patients who may have other risk factors for excessive bleeding from trauma, surgery or other medical conditions, or who are receiving medications known to increase the risk of bleeding (e.g., anticoagulants or antiplatelets used to prevent or treat heart attacks).
   
• Aptivus/ritonavir has been associated with reports of hepatitis and significant liver damage (hepatic decompensation), including some fatal cases. Extra caution is recommended for HIV-positive patients with chronic hepatitis B or hepatitis C, who are at the highest risk of liver-related side effects.
  
  All HIV-positive people receiving Aptivus/ritonavir should be carefully monitored. Liver function tests should be performed prior to starting treatment with Aptivus/ritonavir and rechecked frequently throughout the duration of treatment. HIV-positive people who develop symptoms of liver problems, such as fatigue, loss of appetite, yellowing of the eyes or skin, or liver tenderness, should consult their healthcare providers to discuss stopping Aptivus/ritonavir treatment. HIV-positive people with moderate to severe liver problems should not take Aptivus/ritonavir.
   
• Aptivus, a sulfa-containing drug, should be used with caution in patients with a known sulfa allergy. Mild to moderate rashes and increased sensitivity to the sun (photosensitivity) have been reported in HIV-positive people taking Aptivus/ritonavir. In clinical trials, rash was seen in 14% of females and in 8% to 10% of males receiving Aptivus/ritonavir. Additionally, in one drug interaction trial involving HIV-study female study volunteers who were administered a single dose of an oral contraceptive (ethinyl estradiol) followed by Aptivus/ritonavir, 33% developed a rash. Rash accompanied by joint pain or stiffness, throat tightness, or itching has been reported in both men and women receiving Aptivus/ritonavir. Women taking Aptivus/ritonavir with medications that contain estrogen have an increased risk of developing a rash.
   
• Some people may have large increases in their lipid levels (triglycerides and cholesterol). The long-term chance of getting complications such as heart attacks or stroke due to increases in blood lipids caused by protease inhibitors is not known at this time. Click here for our lesson called "Risks To Your Heart (Hyperlipidemia)".
   
• Diabetes and high blood sugar may occur in people who take Aptivus/ritonavir or other protease inhibitors.
   
• Anti-HIV drug regimens containing protease inhibitors, including Aptivus/ritonavir, can cause abnormal body-shape changes (lipodystrophy; including increased fat around the abdomen, breasts, and back of the neck, as well as decreased fat in the face, arms, and legs). These side effects of anti-HIV drug therapy are reviewed in our lesson on lipodystrophy.

• Aptivus/ritonavir is classified by the FDA as a pregnancy category C drug. Pregnancy category C means that animal studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. HIV-positive women who become pregnant should discuss the benefits and possible side effects of anti-HIV treatment to help protect their babies from HIV (see our lesson called Family Planning, Pregnancy & HIV).
   
• It is not known whether Aptivus/ritonavir passes into breast milk and what effect it may have on a nursing baby. To prevent transmission of the virus to uninfected babies, it is recommended that HIV-positive mothers not breast-feed.

• If you would like to find out if you are eligible for any clinical trials that include Aptivus, there is an interactive web site run by ACRIA, the AIDS Community Research Initiative of America.
   
• Another useful service for finding clinical trials is AIDSinfo.nih.gov, a site run by the U.S. National Institutes of Health. They have "health information specialists" you can talk to at their toll-free number at 1-800-HIV-0440 (1-800-448-0440).