A Pilot Study of Lopinavir/ritonavir Maintenance Monotherapy after Successful Viral Suppression with Standard HAART

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A Pilot Study of Lopinavir/ritonavir Maintenance Monotherapy after Successful Viral Suppression with Standard HAART

HAART has significantly impacted the natural history of HIV infection, but the toxicities and complexities of the components of HAART have limited its effectiveness and safety for many patients. There is a growing need for more effective and simpler HAART regimens.

Earlier experimentation with simplification of HAART by discontinuing NRTIs after achieving viral suppression has failed. This may have been due to the fact that most single PIs are not able to control HIV replication.

Low-dose ritonavir substantially enhances lopinavir plasma levels and lopinavir/ritonavir (LPV/r) [Kaletra] has been shown effective as part of combination therapy in both naive and PI-experienced patients. Furthermore, lopinavir possesses a high genetic barrier to the selection of resistance.

LPV/r monotherapy might have the right combination of potency, favorable pharmacokinetics, and high genetic barrier needed to suppress viral replication and prevent the selection of lopinavir resistance. In the current small pilot study described here, researchers evaluated whether maintenance monotherapy with LPV/r can maintain durable viral suppression after achieving control of viral replication with standard 3-drug HAART.

In this pilot study, six previously treatment-naive patients received therapy with LPV/r 400/100 mg, zidovudine (Retrovir) 300 mg, and lamivudine (Epivir) 150 mg given twice a day for at least 24 weeks with the three most recent viral RNA levels at a value of less than 50 copies/ml.

Treatment with zidovudine/lamivudine was discontinued; treatment with LPV/r was continued with weekly follow-up for the first 8 weeks, every other week for the next 8 weeks, and subsequently every 4 weeks for the remaining 24 weeks of LPV/r monotherapy.

Plasma samples with viral RNA levels of 1000 copies/ml or greater underwent genotypic testing.

The results were compared with those of a baseline genotype obtained before the initiation of LPV/r/zidovudine/lamivudine. All baseline genotypes showed susceptibility to all PI and nucleoside RTI.

Responses to maintenance monotherapy could be characterized as one of two patterns. Patients 1, 2, 4, and 5 maintained viral RNA levels of less than 1000 copies/ml at all times. Of these four patients, viral RNA values were less than 400 copies/ml on 50 out of 53 occasions (94%) and less than 50 copies/ml on 36 out of 53 occasions (68%).

Patients 3 and 6 had less consistent viral RNA suppression with viral RNA levels of 1000 copies/ml or greater at least once. Both patients acknowledged poor adherence to medications throughout this time. Patient 3 had genotypic testing performed at weeks 4, 5, 10, 12, and 14.

None of the protease substitutions associated with decreased susceptibility to lopinavir were identified at any time. As adherence to therapy improved after repeated counseling, the last three viral RNA values were all less than 400 copies/ml. Patient 6 had genotypic testing performed at week 24; only the reverse transcriptase and protease polymorphisms present at baseline were detected.

According to the study authors, these findings are encouraging and suggest that successful therapy of HIV-1 infection is possible with more simple regimens.

The authors conclude, “The simultaneous use of three agents has been and continues to be the standard of care for the treatment of HIV-1 infection. However, more potent antiretroviral agents may obviate the need for three active drugs for all patients.”

“Obviously, large, prospective, and controlled studies are needed to investigate this and are, in fact, ongoing (S. Brun, Abbott Laboratories, personal communication). The potential for a significant paradigm shift in antiretroviral therapy exists and is certainly worth exploring.”

Division of Infectious Diseases, University of Miami School of Medicine, Miami, FL, USA and Abbott Laboratories, Abbott Park, IL, USA.

03/20/05

Reference
R E Campo and others. Lopinavir/ritonavir maintenance monotherapy after successful viral suppression with standard highly active antiretroviral therapy in HIV-1-infected patients (Correspondence). AIDS 19(4): 447-449. March 4, 2005.

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