Aptivus – brand name

tipranavir – generic name

Aptivus belongs to a class of HIV drugs called protease inhibitors (PIs). It is the first approved non-peptide PI.

The PIs block protease, a protein that HIV needs to make more copies of itself. This may slow down HIV disease.

The Food and Drug Administration (FDA) has approved Aptivus for use in combination with other HIV drugs for the treatment of HIV infection in adults who have taken other HIV regimens before or have HIV that is resistant to other PIs. Aptivus is not approved for children.

Aptivus comes in 250 milligram (mg) capsules. Aptivus must be combined with a “booster” dose of Norvir (ritonavir) to increase its potency. The standard adult does is:

• Aptivus 500 mg (two 250 mg capsules) plus Norvir 200 mg (two 100 mg capsules) twice a day.

Aptivus must be used with other medications (in addition to Norvir) to treat HIV.

Aptivus should be taken with food. High-fat meals improve Aptivus blood levels.

Aptivus is a sulfa drug. If you are allergic to sulfa drugs, tell your doctor.

As with all HIV drugs, it is important to take Aptivus as prescribed. Missing or skipping doses can cause your blood levels of the drug to fall too low and resistance can develop. When your virus becomes resistant to an HIV medication, that drug may stop working.

Aptivus is for people who are no longer benefiting from other HIV regimens. It should not be used by people being treated for the first time, unless they have HIV that is already resistant to other PIs.

Aptivus has a different structure than other approved PIs, and may work against HIV that is resistant to these drugs.

Your doctor should use resistance testing and/or treatment history to help determine whether Aptivus is likely to work for you.

In clinical trials, Aptivus worked better when combined with Fuzeon (T-20).

If your virus develops resistance to Aptivus, then it may stop working or not work as well for you. You also may not get as much benefit from other PIs.

Sometimes taking more than one medication can cause drug interactions. Aptivus interacts with many other drugs including some other HIV drugs, anti-fungals, TB drugs, cholesterol-lowering drugs, antidepressants, drugs to treat erectile dysfunction (such as Viagra), several antihistamines, sedatives, and methadone. Taking Aptivus with these drugs can change the amount of each drug in your blood. Your doctor may need to either adjust the doses of your drugs to avoid under- or overdosing or change the drugs you currently take.

Aptivus can decrease the amount of some other PIs, including Lexiva (fosamprenavir), Kaletra (lopinavir/ritonavir), and Invirase (saquinavir) in your blood. Aptivus should only be used cautiously with other PIs (except Norvir).

Aptivus may decrease the effectiveness of birth control pills, so alternative birth control methods should be used.

Certain medications (including some used to treat migraines, insomnia, heartburn, stomach problems, and heart problems) and the herb St. John’s wort should not be taken with Aptivus.

Aptivus contains a small amount of alcohol. Taking Aptivus with Antabuse (disulfiram) and certain other drugs can cause serious illness.

Be sure your doctor knows about all the medications you are taking (including over-the-counter, prescription, street drugs, and herbs), even if you only use them occasionally.

For more information and additional resources to check interactions between the particular drugs you are taking, see our info sheet on drug interactions.

Aptivus was recently approved, and has not been used by as many people as other HIV drugs. Most people tolerate Aptivus well, but it is more likely than other PIs to cause liver problems and high blood fat levels. It is possible that unexpected long-term side effects could show up later.

If you do experience any side effects from Aptivus, they are likely to be temporary and go away as your body adjusts to the medication. If you experience any of the side effects listed below, call your doctor for advice. Do not just stop taking your medication.

• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Fatigue (unusual tiredness)
• Headaches

More serious side effects:

• Bleeding in the brain or intracranial hemorrhage (ICH): Aptivus may increase the risk of bleeding in the brain, which can be fatal. Aptivus should be used with caution in patients who have other risk factors for bleeding due to trauma, surgery, or other medical conditions, or who are taking medications such as antiplatelet agents or anticoagulants ("blood thinners") that may increase the risk of bleeding. Report any unusual or unexplained bleeding to your doctor.
• Liver toxicity: this may be indicated by elevated liver enzymes (ALT and AST), yellowing of the skin or eyes (jaundice), excessive tiredness, and loss of appetite. Severe liver problems are more common with Aptivus than with other PIs. Liver function tests should be performed when starting Aptivus and monitored frequently throughout the duration of treatment, especially in people co-infected with hepatitis B or C.
• Lipodystrophy, which may include elevated blood sugar (glucose), elevated lipid levels ( cholesterol and triglycerides), and fat gain or loss in certain areas. Aptivus increases cholesterol and triglycerides more than other PIs. The exact causes of lipodystrophy are not known, but may include HIV and/or HIV drugs. It is unclear if Aptivus will cause or impact other symptoms of lipodystrophy. For more information on lipodystrophy, see our info sheet.
• Skin rash, which may be accompanied by symptoms such as itching, throat tightness that makes breathing difficult, or joint pain. This side effect is more likely in women taking birth control pills.
• Hypersensitivity reaction: Aptivus contains an ingredient called sulfa, which can cause an allergic reaction in some people. If you are allergic to Bactrim or Septra, you have a sulfa allergy and should use caution with Aptivus.

If you are experiencing persistent, unusual, or serious side effects, call your doctor right away.

Aptivus is a new protease inhibitor, and has not been studied in as many people as the older HIV drugs.

Studies of Aptivus pharmacokinetics (how the drug is processed by the body) show that the drug behaves similarly in the bodies of women and men, but that concentrations of Aptivus reach higher levels in women.

Two studies, 1182.12 and 1182.48 (also known as RESIST 1 and RESIST 2) compared Aptivus plus Norvir to other boosted PIs in people who had taken several HIV drugs in the past, had HIV that was resistant to other PIs, and whose current HIV regimens had stopped working. These studies included about 12% percent women: 139 women out of 1,159 total participants. After 24 weeks, about twice as many subjects taking Aptivus had a significant drop in viral load compared with those taking other boosted PIs (40% vs 18%). However, people in the Aptivus group were more likely to experience liver toxicity.

In clinical trials, skin rash was seen in 14% of women and 8-10% of men taking Aptivus plus Norvir. The risk of developing a rash was higher in women taking birth control pills or hormone replacement therapy that contains estrogen. In one drug interaction study, one-third of HIV-negative women volunteers who took Aptivus with birth control pills developed a rash.

Some studies suggest that the metabolic side effects associated with protease inhibitors may be somewhat different in women and men. For example, some research indicates that women are more likely to gain body fat in their breasts and belly, while men are more likely to lose body fat in their arms, legs, and faces.

The RESIST studies are continuing, and the manufacturer plans to study Aptivus in more HIV+ women and in children.

Studies have shown that pregnant women who use HIV drugs can greatly reduce the risk of passing HIV on to their babies. There have been no formal studies on the use of Aptivus during pregnancy.

Check with your doctor about the best treatment options for you and your baby if you are pregnant or thinking of getting pregnant.

Click this link for more information about pregnancy.

People who are starting HIV treatment for the first time may develop Immune Reconstitution Syndrome or IRS (also called Immune Reconstitution Inflammatory Syndrome or IRIS). IRS can happen as a result of the immune system getting stronger and responding to an HIV-related infection such as Mycobacterium avium infection (MAC), cytomegalovirus (CMV), Pneumocystis jirovecii pneumonia (PCP), or tuberculosis (TB). People may have been treated for these infections in the past or not even know they have them. If you notice any unusual symptoms soon after starting HIV drugs for the first time, let your doctor know right away so you can be evaluated and, if necessary, treated.

1		Cahn, P., et. al. (2004). 24-week data from RESIST 2: phase 3 study of the efficacy and safety of either tipranavir/ritonavir (TPV/r) or an optimized ritonavir (RTV)-boosted standard-of-care (SOC) comparator PI (CPI) in a large randomized multicenter trial in treatment-experienced HIV+ patients. 7th International Congress on Drug Therapy in HIV Infection. Glasgow, Scotland. Abstract PL 14.3.
2		Cooper, D., et. al. (2005). 24-week RESIST study analyses: the efficacy of tipranavir/ritonavir (TPV/r) is superior to lopinavir/ritonavir (LPV/r) and the TPV/r treatment response is enhanced by inclusion of genotypically active antiretrovirals in the optimized background regimen (OBR). 12th Conference on Retroviruses and Opportunistic Infections. Boston, MA. Abstract 560.
3		Hicks, C., et. al. (2004). RESIST-1: a phase 3, randomized, controlled, open-label, multicenter trial comparing tipranavir/ritonavir (TPV/r) to an optimized comparator protease inhibitor/r (CPI/r) regimen in antiretroviral (ARV) experienced patients: 24-week data. 44th Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC. Abstract H-1137a.
4		Yong, C., et. al. (2005). Population pharmacokinetic assessment of systemic steady-state tipranavir concentrations for adults administered tipranavir/ritonavir 500/200 mg twice daily. 12th Conference on Retroviruses and Opportunistic Infections. Boston, MA. Abstract 654.