New Data Support Power and Ease of Use

Twice-Daily Dosing Enhances Convenience, Adherence

SAN FRANCISCO 27 September 1999 - A new study has found that patients treated with VIRACEPT^® (nelfinavir mesylate) prior to other protease inhibitors (PIs) are less likely to develop cross-resistance to other PIs even if HIV resistance to VIRACEPT develops. Information about favorable cross-resistance can help physicians and patients make treatment decisions to maximize the power and durability of anti-HIV regimens while maintaining future options. The study presented here today looked at all currently available protease inhibitors and found varying degrees of cross-resistance: prior use of indinavir was associated with greater cross-resistance than prior use of VIRACEPT or the other PIs studied.

Cross-resistance refers to the phenomenon in which a virus' ability to resist the antiviral effects of one drug also enables it to resist the effects of others in the same class.

"Since many patients fail an initial antiretroviral regimen, it is clear that we must use the drugs we have as wisely as possible," said Richard Haubrich, M.D., Associate Adjunct Professor of Medicine at the University of California, San Diego and lead investigator of the study. "As we learn more about the specific resistance profiles individual drugs, we can use agents that may be less likely to limit a patient's future therapy options. Development of antiretroviral resistance could be considered when designing treatment regimens in order to ensure longer-term benefit for patients."

The multicenter California Collaborative Treatment Group study examined differences in protease inhibitor phenotypic susceptibility after failure of a patient's first PI-containing regimen. The trial studied 116 patients with a median HIV RNA of 4.1 log₁₀ copies/ml and a median CD4 cell count of 295 cells/mm³; 96 patients had received prior PI therapy. In patients previously treated with VIRACEPT, 84%of viral isolates remained susceptible to FORTOVASE^® (saquinavir) and 83% to amprenavir.

Only 29% of patients who had received VIRACEPT had reduced susceptibility to 2 or more PIs; 70% of patients with prior indinavir experience had reduced susceptibility and 43% with other prior PIs had reduced susceptibility (p=0.001).

VIRACEPT Helps Improve Patient Adherence, Study Shows

Using powerful protease inhibitors that are both well-tolerated and convenient for patients has become the new "gold standard" in HIV. A study presented at ICAAC demonstrates the powerful antiviral activity and tolerability of VIRACEPT while confirming its convenience advantage compared to other protease inhibitors – an advantage that can help patients get the maximum benefit from treatment.

The study, presented by Dr. B. Roca of the General Hospital, Castellon, Spain, included 112 treatment-experienced patients randomized to one of two arms: VIRACEPT + d4T + 3TC or indinavir + d4T + 3TC. The VIRACEPT and indinavir groups showed significant difference in their actual drug adherence levels. At 6 months, 70% of patients taking VIRACEPT were adequately adherent, while only 48% of the indinavir group demonstrated adequate adherence (p = 0.0311). Side effects also proved to be a factor in adherence, with only 12% of those on VIRACEPT discontinuing their participation by 6 months while 34% of patients on indinavir discontinued their drug regimen during the same period.

The researchers conclude that while the efficacy of both regimens was similar, those on the VIRACEPT-containing regimen displayed a stronger level of adherence, which may translate into longer lasting clinical benefit when compared to those receiving indinavir.

VIRACEPT Continues to Show Flexibility in Twice-Daily Dosing

Adding further weight to the convenience advantage of VIRACEPT, a study presented here added to the growing body of data supporting VIRACEPT in a twice-daily dosing regimen. Twice-daily, or BID, dosing gives patients much greater flexibility and freedom while making it easier to adhere to their treatment regimens overall.

Data presented by R. Clark, M.D., at Louisiana State University from a 48-week prospective study known as the Women First Study evaluated the combination regimen of VIRACEPT 1250-mg BID + FORTOVASE 1000-mg BID + standard doses of d4T and 3TC; this regimen was compared to a similar three-times-a-day (or TID) arm. An intent-to-treat analysis of the data found that the BID arm was more effective than the TID arm in reducing viral load (HIV RNA <50 copies/ml = 67% vs. 50%, respectively) and had similar effect in raising CD4 cell counts (182 cells/mm³ vs. 170 cells/mm³, respectively).

Protease Inhibitors Suppress Viral Load Longer Than NNRTIs

Julio Montaner, M.D., St. Paul's Hospital, Vancouver, presented retrospective data from a study that found that triple-drug regimens containing a protease inhibitor led to a more durable suppression of HIV viral load than the "protease sparing" regimens that withheld the PI and used an NNRTI instead.

Data on 151 patients on triple therapy from the INCAS (AZT + ddI + nevirapine), AVANTI 2 (indinavir + AZT + 3TC), and AVANTI 3 (VIRACEPT +AZT + 3TC) trials with an HIV-RNA nadir between 20 and 400 copies were combined into a single database. After controlling for baseline differences in viral load, CD4 count, and adherence among the three trials, there were statistically significant differences in the times viral load remained below 500 copies/ml, below 1,000 copies/ml, and
1 log₁₀ below baseline level.

Among the patients who were between the limit of quantification and
400 copies/ml, those assigned to either protease inhibitor-containing regimen had longer virologic suppression than those assigned to AZT + ddI + NVP, the NNRTI-containing regimen.

VIRACEPT is marketed outside the U.S. and Canada by F. Hoffmann - La Roche Ltd of Basel, Switzerland.