Basel, 18 December, A top HIV clinician is stating that strategic antiretroviral planning is more critical than ever in light of the rapidly increasing emergence of HIV 'superbugs'. The doctor is a lead investigator in a study called SWATCH (Switching Antiretroviral Therapy Combinations against HIV) that has been looking at HIV drugs to use early on in the disease and the development of viral resistance. The study has shown that initial HIV therapy with the protease inhibitor Viracept� (nelfinavir) is as effective as the NNRTI efavirenz, while retaining the benefit of further treatment options for patients within its class of drug.

Presenting SWATCH, Charles Boucher, MD, PhD, Clinical Virologist at the University Hospital Utrecht, Netherlands, reinforced the benefit of using Viracept as a first line therapy. �The data from our innovative switching study shows that using Viracept within alternating or continuous initial therapy provides similar efficacy to efavirenz and may minimise the emergence of drug- resistant mutant virus. In light of the data showing Viracept is a highly salvageable first line agent, we anticipate that SWATCH will provide additional long term data to help us strategically select the best first, second and salvage therapies.�

The SWATCH study is an ongoing multicentre international trial which randomised 161 patients to one of three arms:

• d4T + ddi + efavirenz- (arm A)
• AZT+ 3TC + Viracept -twice daily-(arm B)
• Switching between arm A and arm B every 3 months (arm C)

Data was presented on the 161 patients who completed 48 weeks of therapy. The data analysis demonstrated that 100% of patients remaining in the switching therapy arm achieved an undetectable HIV-RNA and similar response rates (85.8% undetectable) were seen in the continuous therapy arms. Drug adherence was equally excellent in all three treatment groups (very good adherence rates were reported by more than 90% of the patients) and a continuous increase in quality of life was measured over the study period. Tolerability and virological failure was similar in both continuous therapy arms. However, continuous treatment with Viracept had the least impact on lipid abnormalities (blood cholesterol and lipids) and did not result in an increase in liver enzymes. A statistically significant elevation in liver enzymes was observed in the continuous efavirenz therapy arm.

Most of the eight patients who failed to respond to therapy on the efavirenz stable arm had developed resistance to efavirenz, leaving no further treatment options from the currently approved members of the NNRTI class of HIV drugs. Of the seven patients on the Viracept stable arm who failed to respond, the majority acquired resistance solely to 3TC (lamivudine) and no new major protease inhibitor mutations were observed - hence retaining the benefit of further treatment options within its drug class. Previous clinical studies have documented that in those circumstances in which HIV no longer responds to Viracept, a high percentage of patients display optimal response to a second line protease inhibitor-containing combination regimen^1,2.

The need for careful therapy planning is due to the growing emergence of HIV viral strains that are highly resistant to all current forms of therapy. An estimated 30-50% of patients under management in Europe and North America have a strain of the virus that has developed resistance to the various antiretroviral treatments currently available. In most cases alternative combinations of HIV drugs can be used to continue the fight against this unforgiving disease. However, reports³ suggest that HIV �superbugs� � commonly known as multi-drug resistant HIV strains � are emerging in Canada. Alarmingly, six cases of newly infected HIV patients whose strain of virus is resistant to all three classes of HIV drugs have been documented and two of these patients have a virus that damages the immune system much faster than normal.

�Considering that there are millions of people living with HIV world-wide, the thought of a �superbug� with no available therapy is untenable,� said Dr. David Reddy, Franchise Leader-Virology, Roche. �Our responsibility as a research based pharmaceutical company is to take the lead in the research and development of HIV medications to ensure we keep one step ahead of drug resistance. Reports about new HIV �superbugs� are an important reminder that we cannot afford to be complacent. New strategies to prolong the use of existing HIV drugs need to be researched as do new therapies to tackle emerging resistance.�

Roche, in conjunction with its Partner Trimeris, is also actively pursuing a completely new approach to HIV therapy with its fusion inhibitors T-20 and T-1249. T-20 is the first in a new class of HIV drugs called fusion inhibitors and it works by preventing the HIV virus from �fusing� with the host cell and taking it over. By focusing on developing a new class of HIV therapies that do not show cross resistance to current therapies, this next generation of HIV drugs has the potential to increase future treatment options for people living with HIV.

- ENDS -

Multi-drug resistant HIV strains or HIV �superbugs� may emerge when people living with HIV find complex daily treatment schedules difficult to strictly adhere to. This can allow the virus to change and make the treatment regimen ineffective. Patients with multi-drug resistant HIV have been identified with virus which reproduces faster than normal, these people have gone from being totally asymptomatic to having very low immune systems in a matter of months.

Headquartered in Basel, Switzerland, Roche is one of the world�s leading research-oriented healthcare groups in the fields of pharmaceuticals, diagnostics and vitamins. Roche�s innovative products and services address needs for the prevention, diagnosis and treatment of disease, thus enhancing people�s well-being and quality of life.

1. TEBAS P, PATICK A. K., KANE E., et al. Virologic responses to a ritonavir/saquinavir containing regimen in patients who had previously failed nelfinavir. AIDS 1999: 13: F23-F28.
2. Zolopa AR, Shafer RW, Warford A, et al. HIV-1 genotypic resistance patterns predict response to saquinavir-ritonavir therapy in patients whom previous protease inhibitor therapy has failed. Ann Intern. Med 1999; 131:813-821

3. New HIV �Superbug� Emerges in Vancouver. Vancouver Sun 2001 August 8

Alexander Watson, Ketchum                           Maria Vigneau, Roche
Telephone: + 44 20 7611 3663                         Telephone: + 41 61 688 9291
                                                                                      + 41 79 506 9941
Email: alexander.watson@ketchum.com           Email: maria.vigneau@roche.com