Project Inform Perspectives 40 - January, 2006

Once-a-day Kaletra

The FDA has approved once-a-day Kaletra (lopinavir + ritonavir) for people taking anti-HIV drugs for the first time. This requires taking six Kaletra capsules every 24 hours, with a small amount of food. This dosing scheme is not recommended for people who have taken other anti-HIV drug combinations in the past.

For more information on this medication—including side effects and drug interactions—read the publication, Kaletra.

New protease inhibitor approved by FDA: Aptivus

On June 22, 2005 the Food and Drug Administration approved the protease inhibitor (PI) Aptivus (tipranavir) for people with extensive anti-HIV drug experience and detectable viral loads. Aptivus, manufactured by Boeringer Ingelheim, must be taken with a low dose of Norvir (ritonavir). It is taken as two 250mg capsules twice a day (total daily dose 1,000mg), along with 200mg of ritonavir twice a day.

Aptivus’ chemical structure is different from other protease inhibitors, and it has been shown to work for people whose virus has developed resistance to other PIs. It is approved only for use by people who have PI resistance and detectable viral loads despite taking anti-HIV drug therapy. The greatest benefits from tipranavir were seen when the drug was combined with Fuzeon (enfuvirtide, T20) in people using both drugs for the first time. Without the addition of Fuzeon, or perhaps some other potent drug a person is still sensitive to, the benefits of Aptivus are quite limited. The combined costs of Aptivus (around $13,000 per year) and Fuzeon (over $25,000 per year) make for an extremely expensive form of treatment which may not be covered by all payers.

For more information on this new treatment option—including side effects and drug interactions—read the publication, Aptivus.

No extended release Zerit after all

Bristol-Myers Squibb (BMS) announced that it will not be moving forward with an extended release version of Zerit (stavudine, d4T), although the Food and Drug Administration (FDA) approved it more than a year ago. The drug is in the same class as Combivir, Epivir (lamivudine, 3TC), Epzicom, Retrovir (zidovudine, AZT), Trizivir, Videx (didanosine, ddI) and Ziagen (abacavir). It is commonly prescribed as a single 40mg pill taken twice a day. The extended release version was a 100mg pill that could be taken once daily. It is likely that the decision not to produce the extended release version of Zerit was heavily influenced by a decision by the committee that develops the guidelines for anti-HIV treatment to add strong warning language about the use of Zerit to the guidelines and move it from the list of preferred anti-HIV drugs to the optional category.

New form of Invirase and no more Hivid

Hoffmann-La Roche has changed the original version of Invirase (saquinavir), which was the first protease inhibitor approved by the FDA. Until recently it had been available only as 200mg hard gel capsules. The new formulation will be sold as a 500mg film-coated tablet. The recommended dose of Invirase is 1,000mg, for use with a small dose (100mg) of Norvir (ritonavir), taken twice a day. Thus, the new formulation reduces the number of Invirase pills from a total of ten per day to just four. The company will no longer sell the soft gel capsule version of the drug. A different formulation of saquinavir, called Fortovase, has been discontinued by its manufacturer.

The company also announced that it will discontinue the anti-HIV drug Hivid (zalcitabine, ddC). This drug is an NRTI in the same class as Combivir, Epivir (lamivudine, 3TC), Retrovir (zidovudine, AZT), Trizivir, Videx (didanosine, ddI), Zerit (stavudine, d4T) and Ziagen (abacavir). Because of problems with potency, side effects, cross-resistance and drug interactions, Hivid is rarely if ever prescribed as part of an anti-HIV treatment regimen.

Caution and dose adjustments for Videx + Viread

In late 2004, the companies that make Videx (didanosine, ddI) and Viread (tenofovir, TDF) issued a letter to doctors regarding the combined use of the drugs. The letter urged doctors to use a great deal of caution before prescribing Videx and Viread together with either Sustiva (efavirenz) or Viramune (nevirapine) in people with very high viral loads.

The basis of this caution were data showing a poor treatment response in some people who started or switched to a new three-drug combination that included these two drugs. Specifically, it was found that people who started therapy with the Videx + Viread combination in addition to either Sustiva or Viramune were more likely to have viral failure than people who started therapy with two other NRTIs in addition to Viramune or Sustiva. This was particularly true for people who started therapy with a high viral load (greater than 100,000), a lower CD4+ cell count (less than 200) and/or history of an AIDS-defining infection.

Additionally, data were presented in 2004 showing that people who start or switch to a combination including Videx and Viread actually had drops in their CD4+ cell count rather than an increase. Though the reasons for poor responses to this combination are not yet clear, it has been found that when people reduce the dose of Videx from 400mg per day to 250mg per day, they do not experience the CD4+ cell count decrease when using the combination. However, even when the dose of ddI is reduced to 250mg per day and combined with Viread, the combination should only be used by people whose viral load is under 100,000.

The bottom line on Videx + Viread:

1. People who have never taken anti-HIV therapy, and whose viral load is over 100,000, should not start a regimen containing a combination of Videx and Viread.

2. People who are thinking of starting or switching to a regimen that includes Videx and Viread should reduce the dose of ddI to 250mg per day.

3. People who are currently on a regimen containing both Videx and Viread should speak with their doctor about this information and make an informed choice about whether or not to continue using the combination, to reduce the dose of Videx, or to switch to a different regimen.

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