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Does Viramune = Sustiva?
by Enid Vázquez
Many doctors have long thought
that Viramune was just as potent as Sustiva, but they didn’t
have good data to back them up. Now it appears that they do.
Still, as usual doctors are disagreeing about the strengths
of the two drugs.
“Did it [study results]
tell us anything we didn’t already know?” said one HIV specialist
who believes both drugs are equally effective. Yet another
said that Sustiva is still the drug to bet on for strength
and durability. He noted that Sustiva may be safer than Viramune.
It has also shown excellent results in many more large clinical
tirals, including superiority over most of the protease inhibitors.
The international 2NN study
was reported at the 10th Conference on Retroviruses and Opportunistic
Infections (CROI) in February, held in Boston. Researchers
found that efficacy in terms of viral load decrease and T-cell
increase was “comparable” between Sustiva and Viramune. “NN”
stands for non-nucleoside, the class of HIV drugs Viramune
and Sustiva belong to.
Overall, about 70 percent
of the people on each drug got their viral load below 50 (undetectable,
or below the level of detection). T-cell increases were around
170. Moreover, many of these people (all taking therapy for
the first time) started with a viral load greater than 100,000,
and Viramune did just as well for them as did Sustiva.
The importance of 2NN is
the strength of the science: it’s a large study (1,216 participants).
It was randomized (people were randomly put into the different
arms of the study, which helps eliminate bias). Plus, it was
a prospective study, which means that it was designed and
then carried out. Several previous retrospective (“look-back”)
studies suggested that Sustiva was more effective than Viramune,
but those studies are not as reliable as prospective clinical
trials.
What else did 2NN show? Ironically,
treatment failure was high—44% for Viramune twice daily and
38% for Sustiva. However, the study used a strict definition
of failure (which is common in clinical trials): less than
one log decline in viral load within three months; viral load
failure after six months (two consecutive viral loads above
50); disease progression or change in therapy. One audience
member thought that the two viral loads over 50 could “bias”
the results, saying that, “In our experience, most people
who go above 50 return to below 50.”
Still, the rate of Grade
3 or 4 (serious) adverse events was high, more than 22 percent
for every combination of drugs. However, the discontinuation
rate for toxicity was the same for both drugs.
The only significant difference
in the rate of side effects was a higher incidence of liver-associated
laboratory abnormalities for Viramune, especially in the once-daily
dose (13.2%). (Once-daily Viramune has not been approved by
the U.S. Food and Drug Administration, or FDA.) But clinical
hepatitis did not differ among the meds.
However, there were two deaths
attributed to Viramune, both in residents of poor countries.
One was related to Stevens-Johnson syndrome and the other
to liver toxicity. A third death occurred due to Zerit. Each
drug combination was given with Zerit and Epivir, which could
be changed due to toxicity. Viramune was given at its FDA-approved
dose of 200 mg (one tablet) twice a day, or the unapproved
400 mg once a day. Sustiva was probably given as three capsules
once a day. (Today it is FDA-approved as one 600 mg tablet
once a day.) A fourth combination, using Sustiva and Viramune
along with Zerit and Epivir, had the highest rate of toxicity,
and the researchers recommended that people not take the two
non-nukes together.
Choosing between Viramune
and Sustiva may have to do with side-effects and toxicity
concerns. A person with a history of mental illness or illicit
drug use may experience higher reates of psychiatric side
effects from Sustiva. These include vivid dreams and sleep
disturbances, and even flashbacks. Sustiva can also raise
cholesterol and triglycerides more than Viramune, though protease
inhibitors tend to have a greater effect on lipids than either
Sustiva or Viramune.
Women may be between a rock
and a hard place. They’re more prone to serious rashes and
liver toxicity with Viramune, both of which can be life threatening.
On the other hand, Sustiva cannot be taken by someone who’s
hoping to become pregnant. It may cause birth defects.
The data from the 2NN trial
are reassuring for people who may need to switch from one
NNRTI to the other because of toxicity or side effects. There
is previous evidence that this strategy works well. And finally,
Viramune is cheaper by about $100 less a month. This might
cause government medical assistance programs, such as ADAP
(AIDS Drug Assistance Program), that are low on funds to push
for Viramune prescriptions over Sustiva.
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