AIDS Treatment Update, Issue 59, November 1997
Edward King

Indinavir is currently prescribed at a dose of 800mg three times daily. An American study compared 1000mg twice daily or 1200 mg twice daily instead. Preliminary results found no significant differences in antiviral effects or side-effects during 20 weeks of treatment.

However, other presentations highlighted the person-to-person variability of indinavir levels. Even with three times daily dosing, at their lowest point between doses (known as the `trough' level) some people's blood levels of indinavir drop perilously close to the level at which they would only incompletely suppress HIV and might allow resistance to develop. For these individuals, a twice daily regimen might result in even lower trough levels, increasing the risk of treatment failure. It is important to remember to drink plenty to minimise the risk of kidney stones when taking indinavir.

Ritonavir is currently taken at a dose of 600mg twice daily, but is associated with significant side-effects which are thought to be related to the high levels of drug achieved a couple of hours after each dose. British researchers found that taking a lower dose of 300mg four times daily appeared to maintain drug levels above the level needed to be effective against HIV, but reduced the rate of side-effects. They suggest that this regimen may be a useful option for people who would otherwise have discontinued the standard twice-daily regimen because of its side-effects.

A study of people taking saquinavir (in its current `hard gel' formulation) found that 27% had blood levels that were below the level required for adequate anti-HIV effects, probably because of problems absorbing the drug in the gut. The researchers suggested that people taking saquinavir should have their drug levels monitored. If too little saquinavir is being absorbed, options might include switching to an alternative regimen, or trying to achieve higher saquinavir levels by taking a higher dose, or by combining it with other agents that boost saquinavir levels. These include grapefruit juice that includes the pith or the anti-fungal ketoconazole, both of which have a small effect on saquinavir levels; nelfinavir, which has a moderate effect; or ritonavir which often has a very large effect.

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