Seventh International Congress on Drug Therapy in HIV Infection Glasgow, UK - 14-17 November 2004

Int Cong Drug Therapy HIV 2004 Nov 14-18;7:Abstract No. PL1.2

Pietro L. Vernazza
Infectious Diseases Department of Medicin, Kantons St. Gallen, Switzerland

Since 1996, triple antirietroviral therapy is considered the gold-standard for the treatment of HIV infection. Once a patient has boarded the train of highly active antiretroviral therapy (HAART), treatment is likely to be continued for a very long period if not for the rest of the patient's life. Thus, high levels of adherence must be maintained to limit the development of drug resistant viruses. Even if excellent drug adherence can be maintained, the development of long-term (metabolic and mitochondrial) side effects, remain a major obstacle for life long treatment.

Strategies to limit drug exposure are thus needed. Reduction of drug exposure by structured treatment interruption is still under evaluation but some strategies failed. Another option would be to limit the number of drugs or drug classes.

Some triple NRTI regimens have demonstrated limited activity or have only been successful in the maintenance setting. Protease inhibitor(PI)-only regimens are an attractive strategy in patients suffering from the effects of mitochondrial toxicity of NRTI. Boosting of PIs with ritonavir results in plasma trough levels that are far above the inhibitory concentration (IC₅₀) of HIV for many PIs. Single boosted PI therapies are therefore a reasonable strategy to be evaluated in clinical trials.

Several groups have started to evaluate ritonavir-boosted PI therapies in different setting. Our group has published a 48-week pilot study (n=12) using indinavir as the active agent in a maintenance setting (Kahlert et al, AIDS, 2004). One patient committed suicide after having been diagnosed with CNS-lymphoma (CD4 >600, HIV-RNA undetectable). All other patients (n=11) treated with ritonavir-boosted indinavir maintained an HIV-RNA load <50 cp/ml at week 48 but several HIV-RNA blips (<400) occurred. High rates of nephrotoxicity limit the use of this treatment as a standard trial. Other groups have studied the use of lopinavir/ritonavir monotherapy either in a maintenance setting (Arribas, Bangkok 2004) or even in drug na ?ve patients (Gathe, Bangkok 2004). More studies are ongoing in France (lopinaivr/rit) and Frankfurt (saquinavir/rit) and the US.

In our ongoing continuation study (ATARITMO) with ritonavir-boosted atazanavir (100/300mg) all nine patients who were previously treated in the indinavir-mono study have reached the efficacy endpoint of 24 weeks and all patients maintained their low HIV-RNA load.

Two major concerns remain with the use of PI-mono therapies: Given the high frequency of HIV-RNA blips, the long-term effect of this treatment strategy needs to be evaluated in larger studies. The second concern relates to the poor penetration of some PIs into sanctuary like brain and genital tract. Long-term studies which also investigate the effect of treatment in CSF are warranted.

SESSION 1: TREATMENT STRATEGIES

2004-11-14
PL1.2

Copyright © 2004 - Thomson ACUMED® All rights reserved. Thomson ACUMED® is an intelligent and innovative medical marketing and communications agency – a new division of The Gardiner-Caldwell Group Ltd, part of The Thomson Corporation, located in Tytherington, UK.

Reproduction of this abstract (other than one copy for personal reference) must be cleared through the authors.