The late-breaking session at this conference featured results from a large study called SOLO. In this study, researchers used a new formulation of the protease inhibitor amprenavir (Agenerase). This new formulation, not yet licensed, is called 908 (GW433908) and requires fewer pills than amprenavir (8 pills/day). When 908 is taken with a small dose of another protease inhibitor called ritonavir (Norvir), levels of 908 in the blood rise to higher-than-normal levels. In this particular case, this leads to the possibility of once-daily dosing of 908. In practice, this means two tablets of 908 and two capsules of ritonavir, both taken once daily, with no food or fluid restrictions.

Study Details

Researchers recruited 660 HIV positive subjects and randomly assigned them into two groups, in which they received one of the following protease inhibitors:

• 908: taken once daily
• nelfinavir (Viracept): taken twice daily

All subjects also received twice-daily doses of abacavir (Ziagen) and 3TC (lamivudine, Epivir). At the start of the study, the profile of subjects was as follows:

• average CD4+ count: 170 cells
• average viral load: 63,000 copies

Subjects were monitored for up to 48 weeks.

Results

After 48 weeks, changes in viral load and CD4+ counts were comparable between the two protease inhibitors. More subjects (6%) receiving 908 had higher-than-normal levels of fatty substances (triglycerides) in their blood than did subjects receiving nelfinavir (2%). On the other hand, reports of diarrhea were higher among subjects receiving nelfinavir (16%) vs. 9% among users of 908.

This study shows that it is possible to create protease inhibitors that are taken once daily. Now drug companies need to continue creating and testing once-daily formulations of other anti-HIV drugs.

Reference

1. Schürmann D, Gathe J, Sanne I, et al. Efficacy and safety of GW433908/ritonavir once daily in therapy na?ve subjects (the SOLO study): 48-week results. Sixth International Congress on Drug Therapy in HIV Infection, 17-21 November 2002, Glasgow. Late breaker plenary lecture 14.4.