New IAS-USA Guidelines Support Saquinavir Plus "Mini Doses" of Ritonavir as Part of Dual Protease-Inhibitor Combination Regimen

SAN FRANCISCO – 2 February, 2000 - The evolving demographics of HIV treatment has emerged as a focal point this week at the 7th Conference on Retroviruses and Opportunistic Infections. Up to 66% of patients receiving anti-HIV therapy have progressed from their first anti-HIV combination and are now receiving their second regimen or beyond, according to data from the HIV in Europe Therapy Monitor conducted by Isis Research.

Providing effective treatment options for patients who have already experienced virological failure on a triple combination regimen is a major challenge for physicians. The combination of the protease inhibitor saquinavir with ritonavir has been used widely in this group, and new data presented this week address how this drug combination can best be used to achieve optimal responses in treatment-experienced individuals. The optimized soft-gel formulation of saquinavir is marketed as FORTOVASE®.

"We’re all aware of major treatment advances like the introduction of protease inhibitors that have redefined HIV treatment and have helped people survive with this disease," said Julio Montaner, M.D., St. Paul's Hospital, Vancouver. "But as patients live longer on treatment, it becomes even more important that we develop data to support the right decisions, to ensure that they continue to benefit for the long term. Using the drugs we have wisely and leveraging everything we know about safety, efficacy, tolerability and resistance are critical to ensuring that patients remain healthy."

Along these lines, data were presented from the ACTG 359 study in which patients who had experienced treatment failure with indinavir plus nucleoside analogues (NAs) were switched to several different regimens, including those containing FORTOVASE plus ritonavir in combination with either delavirdine (a non-nucleoside reverse transcriptase inhibitor, or NNRTI) and/or adefovir dipivoxil.

The ACTG 359 data indicate that early patient response to treatment with FORTOVASE plus ritonavir is a predictor of longer-term success. After 48 weeks of therapy, 59% of patients in this study who achieved a clinically significant virological response at 16 weeks had sustained HIV suppression below 500 copies/mL. Furthermore, the arms containing delavirdine – which like ritonavir also boosts blood levels of saquinavir (the active ingredient in FORTOVASE) – showed greater treatment responses than the arms with adefovir.

These results support encouraging data from three separate studies presented recently showing that FORTOVASE plus ritonavir twice daily (or BID) can provide good response in patients who have previously experienced diminished response to VIRACEPT therapy, with HIV suppression below quantification (400–500 copies/mL) in 65% to 71% of patients at 24 weeks or later.

While the FORTOVASE plus ritonavir combination has high antiretroviral potency, the new IAS-USA treatment guidelines for adults point out that full-dose ritonavir treatment is associated with adverse effects that limit long-term adherence, and that future use of ritonavir is likely to occur in combination with other protease inhibitors. A reduced ritonavir "mini dose" of 100–200mg in twice daily dosing increasingly is being used because of the pharmacokinetic advantages. The combination of FORTOVASE plus mini-dose ritonavir is further optimized by reducing the potential for ritonavir-associated toxicities.

"The new IAS-USA guidelines highlight the importance of choosing treatments that are well-tolerated and easy to take, as well as selecting the most powerful treatment options, so that the patient can receive maximum benefit," said Michael Saag, M.D., director of HIV outpatient care at the University of Alabama at Birmingham.. "The data we’ve seen so far suggest that dual combination protease inhibitors are good candidates to meet all these criteria."

Adding to the database of information on the combination of saquinavir plus mini-dose ritonavir, another study recently was published on the combination of INVIRASE® (saquinavir mesylate) 1000mg plus ritonavir 100mg twice daily plus the NNRTI efavirenz and two NAs. The study enrolled a heterogeneous population of highly treatment-experienced patients who had previously suffered virological failure on indinavir or ritonavir, but had not received NNRTIs or saquinavir previously. At 24 weeks, 71% of patients achieved viral suppression to levels below the limit of quantification (500 copies/mL), and the median CD4 cell count increased by 62 cells/mm3. This saquinavir plus mini-dose ritonavir combination was reported to be well-tolerated.

In its new guidelines, the IAS-USA highlighted the need for physicians to aggressively monitor patient adherence and response to current treatments and rapidly adjust therapy when patients begin to show diminished response to a given regimen, taking emerging information on resistance into account.

As part of Roche’s commitment to helping physicians and patients make the best possible treatment decisions, the company has announced a new program, FortoGene, in a number of countries worldwide. FortoGene couples resistance testing technology with new software to help physicians and patients interpret and leverage complex resistance data prior to selecting a specific treatment regimen. Physicians participating in this new initiative will be able to offer their patients individualized regimens with the goal of achieving an optimal and sustained response to therapy for each patient. FortoGene will be launched in coming months in Italy, Spain, Mexico, Belgium, Germany, Poland, China (Hong Kong), the Netherlands, Argentina, Denmark, and the U.K.

Progress Continues on T-20, An Investigational Treatment for Experienced Patients

While technology is emerging to help physicians and patients maximize the benefit of available treatments, new classes of anti-HIV drugs may offer hope for people who have experienced failure on multiple previous regimens. Progress continues to be reported on the development of T-20, the first of an entirely new class of anti-HIV treatment called fusion inhibitors being developed jointly by Roche and Trimeris. Fusion inhibitors block entry of HIV into the human cell, preventing the virus from commandeering the cell’s machinery to make more copies of HIV.

The preliminary data presented on T-20 show that the presence of antibodies recognizing T-20 does not appear to impact its effectiveness in patients receiving long-term T-20 therapy when compared to patients on T-20 who were antibody-negative. Importantly, the presence of antibodies was not associated with the occurrence of serious adverse events.

These new T-20 data follow information presented at last year’s ICAAC conference that illustrated the positive impact of T-20-containing therapy in reducing HIV viral load in treatment-experienced patients. For more information on T-20 studies to date, log on to

In addition to clinical advances, Roche and Trimeris are making progress on the manufacturing of T-20 and T-1249. The companies have announced the successful transfer of methods to the Roche Boulder, Colorado manufacturing facility for the production of large-scale clinical batches. In July 1999, Roche and Trimeris signed an agreement for the full-scale clinical testing and development of T-20 and T-1249.

New Treatment Effective Against a Serious Opportunistic Infection

While the introduction of protease inhibitors also has led to a dramatic reduction in the incidence of AIDS-related opportunistic infections, physicians and treatment advocates remain concerned that patients who are heavily treatment-experienced may once again begin to develop these infections as they become less responsive to anti-HIV therapy. One serious opportunistic infection, cytomegalovirus (CMV) retinitis, can lead to blindness if untreated.

While the incidence of CMV retinitis has declined dramatically in recent years, progress continues to be made in development of a powerful new treatment. Data from an ongoing study of valganciclovir, an investigational, optimized prodrug of CYMEVENE® (ganciclovir) show that oral valganciclovir offers a convenient and effective alternative to CYMEVENE intravenous (IV) administration.

The two compounds were found to provide similar levels of active drug in the blood. Of patients receiving valganciclovir, 72% responded satisfactorily to induction therapy compared to 77% of those receiving CYMEVENE -IV at four weeks. Analysis of baseline CD4 cell count, rise in CD4 count and concomitant use of antiretroviral therapy showed that therapeutic response was similar in both treatment arms. Median time to CMV retinitis progression in patients receiving valganciclovir was 198 days, compared to 120 days for patients receiving CYMEVENE.