December 20, 2000
One anti-HIV drug called ritonavir (Norvir) is used in double protease inhibitor (PI) combinations because ritonavir often boosts levels of the other PIs to such an extent that twice daily regimens become possible. This is the case when ritonavir and saquinavir (Fortovase) are used together and now appears to be a possibility when ritonavir and indinavir (Crixivan) are taken together.
Researchers in Barcelona and Amsterdam have been conducting small, short studies to find out the most effective and tolerable combination of ritonavir with indinavir. In one experiment, Spanish researchers tested 800 mg of indinavir with 100 mg of ritonavir (indinavir/ritonavir) along with AZT and 3TC, all drugs taken twice daily. The researchers used 27 subjects whose average CD4 count was 209 cells and average viral load was 107,000 copies. None of these people had previously been exposed to anti-HIV drugs.
The researchers found that, on average, this combination of indinavir/ritonavir resulted in prolonged levels of indinavir in the blood. Data collected after subjects had been in the study for four months suggested that the combination has potent anti-HIV activity.
Research teams in both cities also tested once daily regimens of indinavir/ritonavir. According to their results, once daily regimens that achieve suitable levels of indinavir in the blood are possible but further research is necessary for reasons we outline below.
There are some important issues to bear in mind when thinking about these two studies. First, despite using relatively healthy subjects, the combination of indinavir/ritonavir was not always well tolerated. Indeed, about 30% of subjects left one of the studies within the first month because of ritonavir-associated side effects such as nausea, vomiting and "taste-intolerance," the researchers stated.
Since ritonavir boosted indinavir levels, subjects were exposed to almost as much indinavir as if they had been taking indinavir at the standard dose and schedule . This means that subjects taking these combinations likely need to continue taking large amounts of fluid daily.
A third consideration is that not all the people taking indinavir/ritonavir once daily achieved the necessary anti-HIV levels of indinavir.
Finally, given that these are small, short studies, trials in larger numbers of PHAs are needed to assess the long-term impact of these combinations, whether taken once or twice daily.
Journal of Acquired Immune Deficiency Syndromes 2000;25:229-235 and pages 236-245.