March 15, 2001
HAART regimens that include combinations of two protease inhibitors (PIs) have been used since the late 1990s when doctors found that the PI ritonavir (Norvir) taken with another PI, saquinavir (Fortovase), boosted levels of saquinavir in the blood. This combination not only ensures high levels of saquinavir but it also prolongs the time that saquinavir remains in the blood. Because of this boosting effect, ritonavir with saquinavir need only be taken twice daily. Ritonavir is often used in combination with other PIs for the same reason.
Another drug that is increasingly being tested with ritonavir is indinavir (Crixivan). When taken with ritonavir, levels of indinavir are increased to the point where both PIs need only be taken twice daily. A major benefit of this is that it would probably increase adherence, as indinavir ordinarily must be taken every eight hours.
Doctors in Thailand presented results from a study where they compared the combination of ritonavir and indinavir taken twice daily to that of indinavir (without ritonavir) taken three times daily. All subjects also took the two nucleoside analogues (nukes) AZT and 3TC in their standard doses and schedules. Doctors enrolled about 104 HIV positive subjects (37 females, 67 males) and divided them into one of the following groups:
At the start of the study, basic lab values for the whole group were as follows:
Before entering the study, subjects had received at least three months exposure to AZT.
After one year, the proportion of subjects in each group who had achieved a viral load of fewer than 50 copies was as follows:
The side effects listed affected the following proportion of subjects in each group:
Nausea and/or vomiting, diarrhea, or abdominal pain:
Less-than-normal levels of red and white blood cells:
Symptoms of kidney stones:
Higher-than-normal levels of the waste product bilirubin:
Higher-than-normal levels of fatty substances in the blood:
In some cases, because of the side effects listed above, subjects had to reduce their dose of protease inhibitors or even stop taking them.
Ritonavir raises levels of indinavir in the blood, making it possible for a twice-daily dosage of these two PIs. The good news: this would most likely lead to increased adherence. The bad news: it appears that prolonged, high levels of indinavir may be associated with an increased risk of kidney stones and other side effects. So, people taking this PI combination should remember to keep drinking a lot of fluid daily, particularly as the weather becomes warmer. Further studies need to be done on the long-term safety of this PI combination.