Long-term maintenance with a single boosted PI

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Researchers in Switzerland, Germany and the US are investigating long-term maintenance regimens consisting of one boosted protease inhibitor in order to reduce toxicities associated with combining multiple drug classes and the costs of long-term treatment.

The first report on the strategy appeared this week at the Second International AIDS Society Conference on HIV Pathogenesis and Treatment in Paris. Swiss and German researchers recruited twelve patients with a median of 32 months prior HAART experience, and simplified their regimens, stopping their nucleoside analogues and retaining indinavir, boosted with a small amount of ritonavir. All patients had viral load below 50 copies/ml at the time of simplification.

No virologic breakthrough above 500 copies/ml was observed in eleven patients followed for 48 weeks. A total of three viral load measurements between 100 and 500 copies/ml were observed in participating patients during the follow-up period (12 followed to 32 weeks), but none were consecutive in the same patient, indicating that they were likely to represent viral blips rather than breakthrough. The authors noted that the number of viral load measurements above 50 copies/ml in this group of patients compared favourably with the frequency and volume of blips in a larger patient population (5% vs 34%, reported by Greub et al, AIDS 2002).

Glossary

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.

pathogenesis

The origin and step-by-step development of disease.

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

maintenance therapy

Taking drugs for a period of time after an infection has been treated, to stabilise the condition or prevent a re-occurrence or deterioration.

creatinine

Breakdown product of creatine phosphate in muscle, usually produced at a fairly constant rate by the body (depending on muscle mass). As a blood test, it is an important indicator of the health of the kidneys because it is an easily measured by-product of muscle metabolism that is excreted unchanged by the kidneys.

No significant changes in body fat distribution as measured by DEXA scan were detected in five patients at week 48.

However, four patients experienced kidney problems as a result of indinavir: three cases of urolithiasis and two cases of elevated creatinine. This suggests that indinavir/ritonavir may not be the best boosted protease inhibitor choice for such a maintenance strategy.

Meanwhile, Abbott Laboratories is conducting a study of simplified maintenance therapy with Kaletra (lopinavir/ritonavir) in people who have previously achieved undetectable viral load on a Kaletra-containing triple HAART regimen.

References

Hupfer M et al. Pilot study: ritonavir boosted indinavir treatment as a simplified maintenance monotherapy for HIV infection. Antiviral Therapy 8 (Suppl 1): S344 (abstract 589), 2003.