Treatment Review, Issue #29 * Winter 1999
Recent studies have looked at ways to make HAART easier to
take. Some of the available anti-HIV drugs are being studied
with new dosing schedules, and several new drugs offer the
promise of once or twice daily dosing.
NRTI: Nucleoside analog reverse transcriptase inhibitor.
Approved NRTIs are AZT (Retrovir), ddI (Videx), ddC (HIVID),
d4T (Zerit), 3TC (Epivir) and abacavir (Ziagen).
NNRTI: Non-nucleoside analog reverse transcriptase inhibitor.
Approved NNRTIs are Sustiva (efavirenz), Viramune (nevirapine)
and Rescriptor (delavirdine).
Protease inhibitors (PIs): Approved protease inhibitors are
indinavir (Crixivan), nelfinavir (Viracept), ritonavir (Norvir)
and saquinavir (Fortovase).
Sustiva (efavirenz) is a newly approved NNRTI anti-HIV drug
that is given just once a day. For a fact sheet on Sustiva, see
ddI (Videx) is a NRTI drug that's been available for several
years. Several small studies have investigated once daily
dosing of ddI, usually at 300 or 400mg a day, dependent on body
weight. The results suggest that ddI works as well taken once a
day as it does when taken twice a day. Based on these results,
some doctors are already prescribing ddI once daily, although
this has not yet been officially approved by the US Food and
Drug Administration (FDA). The company that makes the drug,
Bristol Myers-Squibb, is waiting for results of a large study
of once daily ddI before asking the FDA if they can change the
currently recommended dosing.
Viramune (nevirapine) is an approved NNRTI drug that may work
when given once a day. The standard dose is 200mg taken once a
day for two weeks followed by 200mg taken twice a day. A study
presented at the 1998 International AIDS Conference in Geneva
looked at 123 people that took Viramune at a dose of 400mg once
a day. The blood levels of Viramune in these people stayed 250
times higher than the amount needed to block 90% of HIV
production in the test tube. This study suggests fairly
strongly that nevirapine could be given once daily. Like with
ddI, the FDA has not yet approved once-daily dosing of
3TC (Epivir) is a twice daily NRTI drug that may have the
potential for simpler once daily dosing. This suggestion is
based upon the length of time the drug stays inside cells in
the body after each dose, as opposed to how much you can
measure floating free in the blood. Two recently presented
studies have used 300mg of 3TC dosed once daily instead of
splitting it into two 150mg doses over the course of the day.
All-in-all, once daily dosing of ddI, 3TC and nevirapine looks
very promising. It's important to realize that these studies
were based on what's already known about these individual
drugs. Not all drugs can simply be switched from three times a
day dosing to twice a day, or from twice day to once a day. The
anti-HIV drugs AZT, d4T, and abacavir, for example cannot be
dosed once a day because they don't stay in the body long
Simpler Dosing: Twice-Daily Drugs
Viracept is a protease inhibitor that's already approved for
treating HIV. The approved dose is 3 pills (750mg) taken three
times a day. Several studies have now compared the approved
dose to a simpler dosing schedule of 5 pills (1250mg) taken
twice a day. After up to 48 weeks of treatment, the studies
have found that Viracept can work just as well given
twice-daily. It's likely that the company that makes Viracept
will soon ask the Food and Drug Administration to approve this
easier dosing schedule, but at the moment twice daily dosing of
Viracept is still considered experimental.
Fortovase is the new version of the protease inhibitor
saquinavir. The approved dosing of Fortovase is 6 pills
(1,200mg) three times a day. Early results of a study comparing
the approved dose to a new dose of 8 pills (1,600mg) twice
daily were recently presented. Both doses were given along with
two NRTI anti-HIV drugs. After eight months of treatment, there
is not a big difference between the doses in terms of increases
in T4 counts and reduction in viral load. However, eight months
may be too soon to tell if the twice daily dosing will work as
well as three times a day over the long term.
Norvir + Fortovase is the most commonly used combination of
protease inhibitors. Norvir boosts Fortovase levels and allows
both drugs to be taken twice-daily, at lower than normal doses.
When combined, Norvir and Fortovase are usually both given at a
dose of 400mg twice daily. The Public Health Service HIV
Treatment Guidelines include Norvir + Fortovase as a reasonable
first-line treatment combination. The guidelines recommend that
Norvir + Fortovase be used in combination with one or two NRTI
Other combinations of protease inhibitors that allow
twice-daily dosing are also under investigation. Studies of
Norvir + Crixivan, Viracept + Fortovase, Crixivan + Viracept
and Norvir + Viracept are ongoing.
Not all studies of simpler dosing have been successful. A study
of the protease inhibitor Crixivan (indinavir) given
twice-daily was recently stopped. The twice daily dose did not
work as well as the standard dose of Crixivan, which is 800 mg
every 8 hours. After six months, 91% of people in the standard
Crixivan dose group had viral loads below 400 copies
("undetectable" on the standard test), compared to 64% of
people taking the experimental twice-daily Crixivan dose. The
first study of standard dose Crixivan combined with AZT and 3TC
has now been going on for three years. A recent update found
that 20 of the 30 people taking this triple combination have
viral loads less than 50 copies after three years of treatment.
The average increase in T-cells so far is 198. This study shows
that Crixivan works best at the standard dose of 800 mg every 8