The effect of plasma drug concentrations on HIV-1 clearance rate during quadruple drug therapy.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

The effect of plasma drug concentrations on HIV-1 clearance rate during quadruple drug therapy.

AIDS. 1998 Jul 30;12(11):F111-5. Unique Identifier : AIDSLINE MED/98372105
Hoetelmans RM; Reijers MH; Weverling GJ; ten Kate RW; Wit FW; Mulder JW; Weigel HM; Frissen PH; Roos M; Jurriaans S; Schuitemaker H; de Wolf F; Beijnen JH; Lange JM; Department of Pharmacy and Pharmacology, Slotervaart Hospital,; Amsterdam, The Netherlands.

Abstract: OBJECTIVE: To investigate the relationship between exposure to antiretroviral drugs and the initial decline of plasma HIV-1 RNA. DESIGN: Open-label study in antiretroviral-naive HIV-1 infected patients using a quadruple drug regimen [nelfinavir (NFV), saquinavir (SQV), stavudine, and lamivudine]. METHODS: The elimination rate constant (k) for HIV-1 clearance was calculated during the first 2 weeks of treatment in 29 patients. Exposure to NFV and SQV was quantified on each study visit. Observed NFV and SQV concentrations were related to those expected in a reference population and a concentration ratio was calculated. The median concentration ratios for NFV and SQV, the baseline CD4+ lymphocyte count and baseline log10 HIV-1 RNA were correlated with k. RESULTS: A significant positive correlation was observed between k and the median NFV (P = 0.001) or SQV concentration ratio (P = 0.016) in univariate analysis. In multivariate analyses, the median NFV concentration ratio remained significantly correlated with k. CONCLUSIONS: The variation in the rate of decline of plasma HIV-1 RNA between patients after the initiation of a quadruple drug regimen could be explained by differences in exposure to NFV or SQV. Determination of k could be used to optimise further antiretroviral drug therapy and may be a first tool to assess antiretroviral activities of new or increasing doses of drugs administered in combination regimens. Furthermore, our data suggest that exposure to antiretroviral drugs should be incorporated in mathematical models to describe HIV-1 dynamics in more detail.

Keywords: CLINICAL TRIAL JOURNAL ARTICLE MULTICENTER STUDY RANDOMIZED CONTROLLED TRIAL Anti-HIV Agents/BLOOD/*PHARMACOKINETICS/THERAPEUTIC USE CD4 Lymphocyte Count Drug Therapy, Combination Human HIV Infections/*DRUG THERAPY/IMMUNOLOGY/VIROLOGY HIV Protease Inhibitors/BLOOD/*PHARMACOKINETICS/THERAPEUTIC USE *HIV-1/GENETICS Nelfinavir/BLOOD/*PHARMACOKINETICS/THERAPEUTIC USE RNA, Viral/BLOOD Saquinavir/BLOOD/*PHARMACOKINETICS/THERAPEUTIC USE Support, Non-U.S. Gov't
990130
A9911073

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, Gill Foundation, the National Library of Medicine, Quest Diagnostics, Roche and Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 1999. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1999. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .