PI Perspective #40
Enero de 2006 En
inglés
Medicamentos contra el VIH: En breve
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: tipranavir
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 enfuvirtide, or perhaps some other potent drug a person is still
sensitive to, the benefits of tipranavir 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 soft
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 be
selling the soft gel capsule version of the drug. A different formulation
of saquinavir, known as Fortovase, is not affected by this news.
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, ddC 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 Viramune (nevirapine) or Sustiva (efavirenz) 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 Viramune or Sustiva 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 ddI 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
- 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 ddI and tenofovir.
- 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.
- 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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