PI Perspective #26

December 1998     View PDF     En español

Indinavir Twice a Day?

New information from a study of indinavir (Crixivan) has shown that a twice daily dosing regimen is not as effective as the three times daily schedule in maintaining viral suppression. As a result, Merck, the manufacturer, is stopping the part of the study which uses twice daily dosing and has notified community groups, information providers and physicians of the new findings.

Based on these findings, Merck is encouraging everyone using twice daily dosing to switch back to three times daily dosing schedules. The new findings are contrary to a previous, smaller study which suggested that twice daily dosing was at least equivalent to the standard three times daily dosing.

Percent of people with viral load below the limit of detection
Study group	at 16 weeks (287 patients)	at 24 weeks (87 patients)
3 times daily	78%	91%
2 times daily	72%	64%

The study included people who had never previously taken a protease inhibitor, or 3TC (lamivudine, Epivir) and the regimens used included twice or three times daily dosing of AZT (zidovudine, Retrovir), 3TC and indinavir.

After 24 weeks of study, 91% of those receiving three times daily dosing had reached or maintained HIV levels below the limit of detection, whereas only 64% on the twice daily regimen had experienced the same level of viral suppression.

What’s most important is that after only 16 weeks, the twice daily dosing schedule appeared equivalent. By six months, however, the superiority of three times daily dosing became very apparent.

Another regimen under study which might still permit twice daily indinavir dosing is the protease inhibitor combination of ritonavir (Norvir) and indinavir (Crixivan). Preliminary, short-term studies of this regimen appear to show indinavir quite suitable for twice daily dosing, while also eliminating the requirement that the drug not be taken with food.

However, it’s important to recognize this is based on early data, covering a short period in two small clinical trials. Another study using twice daily indinavir dosing is in combination with nelfinavir (Viracept).

Caution about Regimen Changes
It’s possible that more people than ever are currently using the indinavir twice-daily dosing regimen as news from the smaller study preceded the announcement of a shortage in supply of another protease inhibitor, ritonavir (Norvir) capsules. When the supply problem was announced, some people may have begun rethinking their anti-HIV regimens and may have made regimen changes, possibly to an easier-to-use regimen using indinavir twice daily dosing.

The lesson learned here is something that Project Inform has been cautioning about for some time with regard to simpler and easier regimens using current available therapies. When these drugs were approved, the reason they were dosed according to schedules in their label instructions (e.g. three times daily) is because studies demonstrated these schedules were necessary to maintain optimal blood levels of drugs. While certainly people want, need and deserve simpler regimens, simply changing a regimen from three times to twice daily dosing is not the solution.

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