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Prior therapy influences the efficacy of lamivudine monotherapy in patients with lamivudine-resistant HIV-1 infection


Opravil, M; Klimkait, T; Louvel, S; Wolf, E; Battegay, M; Fux, C A; Bernasconi, E; Vogel, M; Speck, R; Weber, R (2010). Prior therapy influences the efficacy of lamivudine monotherapy in patients with lamivudine-resistant HIV-1 infection. JAIDS Journal of Acquired Immune Deficiency Syndromes, 54(1):51-58.

Abstract

BACKGROUND:: The M184V mutation decreases the replication capacity of HIV-1. This prospective study aimed to characterize the virologic and immunologic changes during monotherapy with lamivudine (3TC) in patients with limited options for a fully suppressive new therapy. METHODS:: Clinically stable patients with CD4 cells greater than 300/muL, previous virologic failure, and a M184V mutation were treated with 3TC 300 mg once daily during 48 weeks. The primary study endpoint was time to CD4 cell decrease by 30% or to below 200 cells/muL. RESULTS:: Patients were switched from either a protease inhibitor (PI)-containing highly active antiretroviral therapy (PI group, N = 10) or from reverse transcriptase (RT) inhibitor regimens (RT group, N = 16). Among all 26 patients with a median baseline HIV-1 RNA of 3866 copies/mL and CD4 cell count of 432/muL, the probability of reaching the endpoint after 12, 24, 36, and 48 weeks was 15%, 36%, 57%, and 70%, respectively. The median time to the endpoint was 6.0 months. In the PI versus the RT group, 81% versus 40% reached the CD4 endpoint (P < 0.05); the CD4 decline was -170 versus -99 cells/muL (P < 0.05). The replication capacity of the RT increased from mean 53% to 73% (P < 0.01). The increase in the replication capacity of the protease was greater in the PI group (from 51% to 72%, P = 0.07) than in the RT group (from 70% to 82%, P = 0.32). Mutations detected at baseline reverted partially to the wild type. No new HIV-associated illnesses and no 3TC-related toxicities were reported during the study. CONCLUSIONS:: 3TC monotherapy as a partial treatment interruption did not prevent immunologic deterioration in the majority of patients. It may be considered a temporary maintenance strategy in selected patients failing under RT inhibitors only. Withdrawal of the residual activity of a PI from the failing regimen led to a faster CD4 decline, possibly because of greater increase in the fitness of the protease gene.

Abstract

BACKGROUND:: The M184V mutation decreases the replication capacity of HIV-1. This prospective study aimed to characterize the virologic and immunologic changes during monotherapy with lamivudine (3TC) in patients with limited options for a fully suppressive new therapy. METHODS:: Clinically stable patients with CD4 cells greater than 300/muL, previous virologic failure, and a M184V mutation were treated with 3TC 300 mg once daily during 48 weeks. The primary study endpoint was time to CD4 cell decrease by 30% or to below 200 cells/muL. RESULTS:: Patients were switched from either a protease inhibitor (PI)-containing highly active antiretroviral therapy (PI group, N = 10) or from reverse transcriptase (RT) inhibitor regimens (RT group, N = 16). Among all 26 patients with a median baseline HIV-1 RNA of 3866 copies/mL and CD4 cell count of 432/muL, the probability of reaching the endpoint after 12, 24, 36, and 48 weeks was 15%, 36%, 57%, and 70%, respectively. The median time to the endpoint was 6.0 months. In the PI versus the RT group, 81% versus 40% reached the CD4 endpoint (P < 0.05); the CD4 decline was -170 versus -99 cells/muL (P < 0.05). The replication capacity of the RT increased from mean 53% to 73% (P < 0.01). The increase in the replication capacity of the protease was greater in the PI group (from 51% to 72%, P = 0.07) than in the RT group (from 70% to 82%, P = 0.32). Mutations detected at baseline reverted partially to the wild type. No new HIV-associated illnesses and no 3TC-related toxicities were reported during the study. CONCLUSIONS:: 3TC monotherapy as a partial treatment interruption did not prevent immunologic deterioration in the majority of patients. It may be considered a temporary maintenance strategy in selected patients failing under RT inhibitors only. Withdrawal of the residual activity of a PI from the failing regimen led to a faster CD4 decline, possibly because of greater increase in the fitness of the protease gene.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:May 2010
Deposited On:20 Jan 2010 09:40
Last Modified:05 Apr 2016 13:45
Publisher:Lippincott Wiliams & Wilkins
ISSN:1525-4135
Publisher DOI:https://doi.org/10.1097/QAI.0b013e3181bef889
PubMed ID:19838125

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