Roche has been committed to helping people living with HIV infection since the advent of HIV therapy. The product portfolio began with the development of the ELISA tests and went on to introduce Hivid^� (zalcitabine, or ddC), a reverse transcriptase inhibitor which provides the opportunity to combine antiretroviral agents to combat HIV more effectively.

Roche's ongoing commitment to HIV care led to the introduction of the Roche Amplicor HIV-1 Monitor^�. This market leading technology has redefined clinical management, allowing physicians to directly measure the viral load of individual patients and determine the efficacy of their treatments. In addition, Roche Amplicor has proven to be a valuable tool for drug development and HIV research. Roche molecular systems have continued to develop the Roche Amplicor HIV-1 monitor to detect extremely low levels of virus (50 copies/ml) and variations in HIV-1 subtypes.

In 1995, Roche introduced Invirase^� (saquinavir), the world�s first HIV protease inhibitor that marked a seminal change in the treatment of HIV infection. Only now was it possible to inhibit two different stages of the HIV lifecycle, thus allowing for highly active antiretroviral therapy (HAART). The use of protease inhibitors combined in HAART regimens led to the discovery of 'PI-boosting'. Initial pilot studies using Roche Amplicor found that when Invirase was administered with ritonavir (Norvir^�), a significant increase in saquinavir plasma levels led to highly potent viral suppression. Further clinical trials have shown that saquinavir with a mini-dose of ritonavir at a dose of 1000/100 mg bid provides maximal viral suppression but with a reduction in ritonavir-associated side effects � therefore offering a combination of high efficacy with an outstanding safety profile. Invirase/r 1000/100 mg bid has been approved for use in Europe and in the USA. More recently, Roche has optimized saquinavir with the introduction of a 500 mg tablet (Invirase 500), such that the pill burden is significantly reduced from five to two tablets twice daily (plus one ritonavir capsule). US and EU approval were given in December 2004 and May 2005, respectively.

In 1998 Roche introduced Viracept^�, a new protease inhibitor licensed from Agouron Pharmaceuticals�. Viracept as a first-line therapy preserves future options due to the lack of cross-resistance with other antiretrovirals. The emergence of liver disease as a major cause of mortality has become of increasing importance in the HAART era. This is mainly due to increased survival, the high prevalence of co-infection with HIV and hepatitis C virus (HCV) and the accelerated course of HCV disease in the presence of HIV. For these reasons preserving hepatic function has become an important goal in the overall management of HIV infection. Clinical trials have shown that Viracept is highly efficacious and well tolerated in HIV�HCV co-infected patients.

In 2001, Roche received approval to use Valcyte^�, an oral pro-drug of ganciclovir, to treat CMV in HIV-infected patients providing a more convenient regimen for maintenance therapy.

The growing prevalence of drug-resistant virus in the community means that there is an urgent need for drugs that are active against resistant HIV strains. Roche and Trimeris co-developed FUZEON^� (enfuvirtide), the first of a new class of antiretrovirals with a completely novel mode of action, the fusion inhibitors. Because it acts at a different mechanistic site, FUZEON is active against virus that is resistant to the other three classes of antiretroviral agents (nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors) and is most effective when used in combination with other active antiretrovirals. FUZEON received approval from the US Food and Drug Administration (FDA) in March 2003 and from the European Commission in May 2003.