Newly approved PI provides treatment options
Pros and cons to using nelfinavir up front
The recent Food and Drug Administration approval of nelfinavir (Viracept) brings the number of protease inhibitors now available for HIV treatment to four. Just where nelfinavir fits into the treatment arsenal, however, is not clear. Clinicians may want to see more data before making a decision, researchers say.
Manufactured by Agouron Pharmaceuticals of La Jolla, CA, nelfinavir was approved based on the results of three trials in which the drug alone and in combination with other drugs significantly reduced viral load. Since its approval earlier this year, long-term results have been released on two combination studies.
At the 10th International Conference on Anti-viral Research in Atlanta in March, study results on nelfinavir combined with zidovudine (AZT) and epivir (3TC) showed that virus remained undetectable after 10 months of treatment for 87% of 74 patients. CD4 counts rose in these patients, for a mean increase of 173 cells.
In a smaller clinical study at Aaron Diamond AIDS Research Center in New York City, HIV fell below quantifiable levels for all 10 patients who had taken the same combination for 56 weeks. Staff investigator Martin Markowitz, MD, reported in Atlanta that HIV also was undetectable in the lymphoid tissue in eight of nine patients tested after more than 11 months of therapy, indicating that the combination has good penetration into other parts of the body.
"These data are very promising and suggest that when aggressively treated, HIV infection may be effectively controlled over a long period for most patients," he said.
Nelfinavir appears to have a more favorable side-effect profile than the other protease inhibitors, with diarrhea being the most common adverse reaction.
Seeking clarity over when to use the drug
Faced with limited study data on nelfinavir, many clinicians are unsure where the new drug fits in the current treatment scheme. A major consideration is its resistance and cross-resistance make-up. Early studies indicate that virus that becomes resistant to nelfinavir remains susceptible to the three other approved protease inhibitors. If that is the case, nelfinavir might be a good candidate for initial therapy, says Ronald Barr, director of the San Francisco AIDS Foundation.
"Because its resistance profile is different from the other protease inhibitors, this could be a rationale for starting nelfinavir as the first in combination with other drugs," he says.
Researchers caution against relying too heavily on the preliminary resistance data on nelfinavir, however, especially because there is so little experience with resistance to the drug in human trials.
"The piece we don’t know about yet and could get burned by is the extent to which, if you start with nelfinavir as primary treatment, you can switch to others [protease inhibitors]," says Ken Mayer, MD, director of the AIDS program at Brown University in Providence, RI. "The company makes a claim that I don’t think is adequately substantiated that the most common resistance pattern doesn’t cross-select to ritonavir or indinavir resistance."
On the other hand, Mayer notes that nelfinavir is well-tolerated by his patients and can be taken with meals. "It has some of the best features of ritonavir and indinavir," he adds.
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