Fifth International Congress Drug Therapy in HIV Infection 22-26 October, 2000 Glasgow, UK

EFFICACY OF THE REGENERATING IMMUNE SYSTEM IN THE INHIBITION OF CMV REPLICATION AFTER HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART))

J.R. Deayton, C.A. Sabin, M.A. Johnson, P.D. Griffiths, V.C. Emery
Royal Free and University College School of Medicine, London, UK

Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. 5.4.1
AIDS 2000, Oct 22-26;14(Suppl. 4);S5

Successful HAART results in the reconstitution of both cellular and numeral immune responses against CMV. Consequently, although CMV replication in vivo is highly dynamic, CMV viraemia may be cleared following HAART in the absence of specific anti-CMV therapy. The antiviral efficacy of drugs such as ganciclovir against CMV has been extensively studied. This study therefore aims to estimate the antiviral efficacy of the regenerating immune system in control of CMV replication following HAART. The patients studied had asymptomatic CMV viraemia at baseline. Individuals initiating HAART were compared with controls who received no antiretroviral therapy. None of the patients received anti-CMV therapy at any time prior to or during the study period. Prospective monitoring for CMV viraemia by qualitative PCR was conducted at each clinic attendance; CMV load was measured by quantitative competitive PCR. Log change in CMV load from baseline was calculated for each patient and the median value at specific time points was calculated. The rate of decline of CMV load following HAART was used to calculate the half-life of decline, where decline was assumed to follow an exponential function, y(t) = y(0) e^-kt where y is the CMV load at times 0 and t, and k, the decay constant. Using the knowledge that the doubling time for CMV is approximately one day, these data were used to estimate the efficacy of the immune system at inhibiting CMV replication. Eleven patients were compared with 11 controls. Median baseline CMV load was higher in the HAART group (4.90 log₁₀ copies/ml) than in the controls (2.94 log₁₀ copies/ml). CMV replication was inhibited after HAART with a median decline in CMV load of 1.8 logs at 1 month and 2.6 logs at 6 months. There was no significant change in CMV load in the controls. The half-life of decline of CMV in blood ranged from 1.52 days to 25 days (median 5.61 days). This equates to a mean antiviral efficacy of the immune system of 61.5% (range 52.8–85%).

The calculated mean antiviral efficacy of the regenerating immune system of 61.5% may be compared to that of ganciclovir which has a mean efficacy of 91.5% against wild type CMV. This further explains the protective effect of HAART against CMV disease, even in patients with high CMV loads at baseline. The half-life of decline of CMV DNA in blood after HAART is variable. The factors dictating the half-life are likely to be immune mediated and may include the residual number of precursor cells at baseline or the rate of differentiation of regenerating cells after HAART. Identification of the immune factors mediating this process will provide further insight into the host control of CMV replication.

Presenting author: J.R. Deayton

Download Conferences Abstracts

2000-10-22
5-4-1

Originally published in AIDS Volume 14, Supplement 4 and hosted with permission of the publisher Lippincott Williams & Wilkins, 250 Waterloo Road, London, SE1 8RD, UK. Tel: +44 (0)20 7981 0700 Fax: +44 (0) 7981 0701

Copyright © 2000 - Lippincott Williams & Wilkins. All rights reserved. All abstracts from the Fifth International Congress Drug Therapy in HIV Infection, appearing on the AEGiS web site, are protected by United States copyright law and may not be reproduced, distributed, transmitted, displayed, or otherwise published without the prior written permission of Lippincott Williams & Wilkins. You may not alter or remove any trademark, copyright or other notice. However, provided that you maintain all copyright and other notices contained therein, you may download material (one machine readable copy and one print copy per page) for your personal, non-commercial use only.

http://www.aidsonline.com http://www.ovid.com

This information is designed to support, not replace, the relationship that exists between you and your doctor. ©1980, 2005. AEGiS.