On June 22, the U.S. Food and Drug Administration (FDA) granted accelerated approval of Aptivus (tipranavir), an HIV protease inhibitor. Aptivus created excitement during its development by displaying greater power to cause large drops in viral load in people with drug-resistant virus, compared to people taking other protease inhibitors already on the market.

Unfortunately, it cannot be taken by itself but must be boosted with 200 mg of Norvir (ritonavir), twice a day. This is more Norvir than you take in other boosted regimens, so remember that Norvir has a lot of drug interactions. The Aptivus dose is 500 mg (two 250 mg capsules) and it should be taken with food. It is refrigerated prior to dispensing, and then must be maintained at 77ºF or lower. Like Bactrim and Lexiva, it is a sulfa drug, so watch the sun exposure. In more than 3 out of 100 people taking Aptivus, the adverse reactions were diarrhea, nausea, fatigue, headache and vomiting. Common lab changes were elevated liver enzymes, cholesterol and triglycerides. Mild to moderate rash was observed in 14% of women and in 8-10% of men. In a drug interaction study in HIV-negative women on birth control, 33% developed rash. Be sure to check with your doctor or pharmacist if you are on oral hormones! Women taking estrogen-based birth control pills or patches should take additional or alternative forms of birth control.

There is a black box warning on the drug label, which basically means be sure to go back to see your doctor for follow-up labs after starting this medicine: "Specifically, Aptivus co-administered with low dose ritonavir has been associated with reports of clinical hepatitis and hepatic decompensation, including some fatalities. Extra vigilance is warranted in patients with chronic hepatitis B or hepatitis C co-infection, as these patients have an increased risk of hepatotoxicity."

Aptivus showed better results in clinical trials when it was taken along with Fuzeon (T-20), the only injectible HIV drug on the market. Fuzeon is still the only drug in a class called fusion inhibitors - these stop HIV from getting into cells. The approval of Aptivus is expected to help sales of Fuzeon, because it's difficult for people with advanced HIV disease to find two new drugs they can take together in a combination, and Fuzeon is one of the newer drugs. Plus it's one that people might hold off on because of its route of administration. Aptivus cannot be taken with Kaletra, Agenerase, Reyataz or Fortovase/Invirase, because it lowers the levels of those other protease inhibitors. (It also lowers the levels of Norvir, so you shouldn't see as many gastrointestinal side effects as you normally would with that drug.)

After six months, Aptivus dropped viral load by one log (a significant amount) in 40% of people taking it. In contrast, 18% of those on other protease inhibitor combinations saw this response. These were people who had been on several combination therapies for HIV, so they're less likely to have significant drops in their viral load no matter what medication they take.

You should find out first if your virus is already resistant to Aptivus. Experts recommend drug resistance testing before going on it. Some resistance mutations (33, 82, 84 and 90 - ask your doctor!) that occur may make Aptivus less effective. A treatment history can also help here - certain drugs are associated with certain mutations (mostly when your viral load starts going up while you're still on the medication). Aptivus is expected to be less effective for people with multiple mutations (three or more) (there'll be a letter in front and back of the codon number on your resistance test results, such as L82T). (These codons - also called amino acids - are known as PRAMS, for protease resistance-associated mutations). There are different letters that can wrap around these codon numbers, and some have shown tipranavir resistance while others don't. It's all still being figured out.

From the AIDS Treatment Activists Coalition (ATAC): A steady onslaught of “unreasonable, unacceptable, and unjustified” increases in the price of therapies to treat HIV has caused activists in the U.S. to accuse drugmakers of artificially inflating the market at the expense of people living with HIV/AIDS. As an example, activists point to the recent launch of the new drug Aptivus, a protease inhibitor developed by Boehringer-Ingelheim, which came in at the highest price ever for this class of medication—more than $13,000 per year, which does not include the cost of other medications that must be taken in combination with Aptivus.

“We are approaching the point where a year’s worth of HIV medications in the U.S. will cost anywhere from $30,000 to $50,000 a year. Every time a new medication is made available, it usually comes in at a new higher price than others in its class,” stated Nelson Vergel, a member of the AIDS Treatment Activists Coalition. “The same thing happened with Reyataz, another protease inhibitor made by Bristol-Myers Squibb. It was the first once-daily medication of this kind, and the company priced it at an all-time high, with regular increases since then. It now costs almost $11,000 per year. This behavior is simply unreasonable, unacceptable, and unjustified.”

Howard Grossman, MD, Executive Director of the American Academy of HIV Medicine notes, “Many insurance companies have focused on the high price of drugs to treat HIV. Healthcare providers are finding their choices increasingly limited as higher-priced drugs are taken off ‘preferred’ lists, in some cases raising patient copays from $20 to $75 or more per prescription. Anything that prevents doctors from prescribing the properly-indicated drugs reduces our chance of controlling HIV. High prices are driving this.”

“Sadly, Boehringer-Ingelheim failed to realize that the size of the potential Aptivus market is directly tied to patients’ access through publicly funded programs, and they just made that market a lot smaller,” said Lei Chou, Director of Mobilization at the Community HIV/AIDS Mobilization Project (CHAMP). “State Medicaid Programs will delay coverage of the drug for months, AIDS Drug Assistance Programs will have to place access restrictions or may not cover it at all. This pricing decision will put Aptivus out of reach for the majority of patients who can benefit from it.”

This past summer, the FDA granted tentative approval to several generic versions of HIV drugs—Sustiva (efavirenz); Viramune (nevirapine); Zerit (d4T, stavudine), Retrovir (AZT, zidovudine) and Combivir, which is made up of two HIV drugs: Retrovir and Epivir (lamivudine). With these approvals, the generics will be legally available for purchase by the President’s Emergency Plan for AIDS Relief (PEPFAR). The program’s refusal to buy any drugs without a U.S. patent has been controversial. It drives up the price, benefiting pharmaceuticals at the expense of greater drug access.

According to the FDA, “The agency’s tentative approval means that although existing patents and/or exclusivity prevent marketing of a particular product in the United States, it meets all of FDA’s quality, safety and efficacy standards required for marketing in the United States.” Sustiva is a particularly powerful HIV medication that is popular in the U.S., but it cannot be taken by women wishing to conceive, due to its birth defect profile. The use of single-dose nevirapine for the prevention of mother to child transmission of HIV is permitted under PEPFAR. Zerit has long ago lost favor in the United States because of its strong association with facial wasting.

… but only if you’re taking therapy for the first time. U.S. HIV treatment guidelines from the Department of Health and Human Services were updated in July to add once-daily Kaletra for people who are treatment-naïve. This is a dose of six capsules, and has a significantly greater risk of causing diarrhea (16% vs. 5% for the twice-a-day dose in studies). A new formulation of Kaletra coming soon will probably make the once-a-day dose more tolerable. The once-a-day dose is not recommended for people who have already been on therapy, because it has not been studied in this group and because of a drop in the lowest level in the blood (trough). Nor is it recommended for people taking Sustiva, Viramune, Lexiva, or Viracept.

Also, the guidelines now state that the combination of Videx and Viread with a non-nucleoside analog (either Sustiva or Viramune) should not be given to treatment-naïve people.

Test Positive Aware Network (TPAN), the non-profit HIV service organization that publishes Positively Aware, has teamed up with the International Association of Physicians in AIDS Care (IAPAC) to produce educational materials for both people living with the virus and their medical providers. IAPAC, which like TPAN is also based in Chicago, has long published magazines and other materials for clinicians and patients. The partnership gives Positively Aware the opportunity to reach more medical providers, and to work with an international organization dedicated to treatment education and expanded drug access.

IAPAC produces numerous patient-related publications on a variety of HIV/AIDS topics such as mental health, metabolics, resistance, and antiretroviral therapy updates. It also produces guides and posters that feature guideline-based information through its Guidelines Regimen Information Program (GRIP).

The agreement covers a variety of activities, such as the inclusion of IAPAC materials into Positively Aware and the expanded distribution of Positively Aware to all IAPAC members nationwide..