Protease Combinations: Ritonavir and Indinavir One Year Later

What's New, from the 8th Conference on Retroviruses and Opportunistic Infections

March 15, 2001

This article is part of The Body PRO's archive. Because it contains information that may no longer be accurate, this article should only be considered a historical document.

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:

  • indinavir 800mg with ritonavir 100mg, both taken twice daily

  • indinavir 800mg three times daily

At the start of the study, basic lab values for the whole group were as follows:

  • average CD4+ count -- 168 cells

  • average viral load -- 10,000 copies

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:
  • ritonavir with indinavir -- 64%

  • indinavir alone -- 70%

Side Effects

The side effects listed affected the following proportion of subjects in each group:

Nausea and/or vomiting, diarrhea, or abdominal pain:

  • ritonavir with indinavir -- 24%

  • indinavir alone -- 11%

Less-than-normal levels of red and white blood cells:

  • ritonavir with indinavir -- 12%

  • indinavir alone -- 7%

Symptoms of kidney stones:

  • ritonavir with indinavir -- 6%

  • indinavir -- 4%

Higher-than-normal levels of the waste product bilirubin:

  • ritonavir with indinavir -- 4%

  • indinavir alone -- 0%

Higher-than-normal levels of fatty substances in the blood:

  • ritonavir with indinavir -- 8%

  • indinavir alone -- 0%

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.

Poster 335

This article was provided by Canadian AIDS Treatment Information Exchange. Visit CATIE's Web site to find out more about their activities, publications and services.


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