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CROI 2004; San Francisco, Calif.; Feb. 8-11, 2004

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Learn about a single-tablet HIV-1 regimen that was studied in patients with high and low viral loads >

UNBP0708 06/14

The Body PRO Covers: The 11th Conference on Retroviruses and Opportunistic Infections

Drug Monitoring, NRTI Activity Help Predict Lopinavir/Ritonavir Response in Experienced Patients

February 11, 2004

The inhibitory quotient (IQ) -- defined as the trough concentration of a drug divided by the protein-corrected concentration of that drug required to inhibit 50% growth of the virus -- correlates well with the activity of many antiretroviral agents, especially protease inhibitors (PI). An advantage of lopinavir/ritonavir (LPV/r, Kaletra) is its relatively high IC50 (a measure of the concentration required for 50% inhibition of the virus), due to the marked sensitivity of lopinavir to low-dose boosting with ritonavir (RTV, Norvir). This study sought to explore the effectiveness of two different strategies to increase the lopinavir IQ even further, namely by using a higher dose of the combined lopinavir/ritonavir formulation or boosting levels higher with additional ritonavir.

Thirty-six subjects with multiple-PI experience entered the study, and were randomized to one of two treatment arms: 1) high-dose lopinavir/ritonavir at five capsules (667 mg/167 mg) twice daily, or 2) standard-dose lopinavir/ritonavir at three capsules twice daily with an additional 200-mg twice-daily dose of ritonavir. Plasma samples for lopinavir concentrations were obtained at week three. The study lasted 48 weeks.

At week three, both dosing schemes produced substantially higher lopinavir levels than observed with data from prior studies with standard-dose lopinavir. The use of the five-capsule, twice-daily lopinavir/ritonavir achieved lopinavir trough levels that were 73% higher, while the extra ritonavir strategy achieved trough levels that were 56% higher. The former was also generally better tolerated, with lower rates of diarrhea. Virologic suppression to less than 400 copies was achieved in 64% of the patients in the high-dose lopinavir/ritonavir group versus 58% in the extra-ritonavir group, and 83% of the study subjects overall experienced at least a 1 log HIV RNA reduction. In a multivariate analysis evaluating the predictors of virologic response, both the lopinavir/ritonavir IQ and the number of active nucleosides were independently associated with better viral load reduction.

This study confirms that the baseline resistance profile and drug plasma levels provided by the IQ add additional information about the likelihood of treatment response. It furthermore raises the question of whether therapeutic drug monitoring and subsequent dose manipulation should be introduced into clinical practice, a concept currently being explored in an ACTG study. The finding that baseline NRTI activity also predicted the magnitude of the HIV RNA response was a reminder that in treatment-experienced patients, it is critical to maximize the activity of all components of the regimen whenever possible.

Reference

Abstract: Lopinavir Inhibitory Quotient Predicts Virologic Response in Highly Antiretroviral-Experienced Patients Receiving High-Dose Lopinavir/Ritonavir (Oral 134)
Authored by: R. Bertz, J. Li, M. King, D. Kempf, D. Podzamczer, C. Flexner, C. Katlama, D. V. Havlir, S. Letendre, J. Eron, L. Weiss, J. Gatell, A. Simon, K. Robinson, S. Brun
Affiliations: Abbott Labs., Abbott Park, IL; Hosp. de Bellvitge, Barcelona, Spain; Johns Hopkins Univ. Sch. of Med., Baltimore, MD; Hosp. de la Pitie-Salpetriere, Paris, France; Univ. of California, San Francisco, CA; Univ. of California, San Diego, CA; Univ. of North Carolina at Chapel Hill, NC; Hosp. Europeen George Pompidou, Paris, France; Hosp. Clin., Barcelona, Spain

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This article was provided by TheBodyPRO.com. It is a part of the publication The 11th Conference on Retroviruses and Opportunistic Infections.
 



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