Journal Article

Antiviral Activity of Lamivudine in Salvage Therapy for Multidrug-Resistant HIV-1 Infection

Thomas B. Campbell, Nancy S. Shulman, Steven C. Johnson, Andrew R. Zolopa, Russell K. Young, Lane Bushman, Courtney V. Fletcher, E. Randall Lanier, Thomas C. Merigan and Daniel R. Kuritzkes

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 41, issue 2, pages 236-242
Published in print July 2005 | ISSN: 1058-4838
Published online July 2005 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/430709
Antiviral Activity of Lamivudine in Salvage Therapy for Multidrug-Resistant HIV-1 Infection

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Background. Maximum suppression of virus replication is often not achievable for persons infected with multidrug-resistant human immunodeficiency virus type 1 (HIV-1). Available data suggest that lamivudine contributes to partial viral suppression, despite the presence of M184V mutations and high-level phenotypic lamivudine resistance.

Methods. Selective lamivudine withdrawal was studied in 6 subjects who had incomplete viral suppression during antiretroviral treatment for multidrug-resistant HIV-1 infection.

Results. Plasma levels of HIV-1 RNA increased to 0.5 log10 copies/mL above baseline 6 weeks after the withdrawal of lamivudine treatment (P = .04), even though reversion of lamivudine resistance was not yet detected. Early increases in plasma levels of HIV-1 RNA after lamivudine withdrawal were associated with the presence of the T215Y/F mutation and broad phenotypic resistance to nucleoside reverse-transcriptase inhibitors at baseline. Genotypic and phenotypic reversion of lamivudine resistance was detected in 4 subjects 8–14 weeks after withdrawal of lamivudine therapy. The duration of lamivudine withdrawal ranged from 8 to 22 weeks; all subjects resumed lamivudine treatment. Plasma levels of HIV-1 RNA were 0.6 log10 copies/mL above baseline (P = .03) when lamivudine therapy was resumed. After the resumption of lamivudine treatment, plasma HIV RNA levels decreased to baseline levels in 3 subjects but remained elevated in 3 subjects who had evolution of increased antiretroviral drug resistance during the period of lamivudine withdrawal. Safety concerns raised by this latter finding led to permanent closure of the study.

Conclusions. In select cases of multidrug-resistant HIV-1 infection, lamivudine contributes to suppression of HIV-1 replication, despite the presence of M184V mutations and lamivudine resistance.

Journal Article.  4376 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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