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, Daniel R. Kuritzkes

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)236-242
Number of pages7
JournalClinical Infectious Diseases
Volume41
Issue number2
DOIs
StatePublished - Jul 15 2005
Externally publishedYes

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Salvage Therapy
Lamivudine
Virus Diseases
Antiviral Agents
HIV-1
RNA
Virus Replication
Mutation
Therapeutics
Reverse Transcriptase Inhibitors
Nucleosides
Drug Resistance

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Campbell, T. B., Shulman, N. S., Johnson, S. C., Zolopa, A. R., Young, R. K., Bushman, L., ... Kuritzkes, D. R. (2005). Antiviral activity of lamivudine in salvage therapy for multidrug-resistant HIV-1 infection. Clinical Infectious Diseases, 41(2), 236-242. https://doi.org/10.1086/430709

Antiviral activity of lamivudine in salvage therapy for multidrug-resistant HIV-1 infection. / Campbell, Thomas B.; Shulman, Nancy S.; Johnson, Steven C.; Zolopa, Andrew R.; Young, Russell K.; Bushman, Lane; Fletcher, Courtney V.; Lanier, E. Randall; Merigan, Thomas C.; Kuritzkes, Daniel R.

In: Clinical Infectious Diseases, Vol. 41, No. 2, 15.07.2005, p. 236-242.

Research output: Contribution to journalArticle

Campbell, TB, Shulman, NS, Johnson, SC, Zolopa, AR, Young, RK, Bushman, L, Fletcher, CV, Lanier, ER, Merigan, TC & Kuritzkes, DR 2005, 'Antiviral activity of lamivudine in salvage therapy for multidrug-resistant HIV-1 infection', Clinical Infectious Diseases, vol. 41, no. 2, pp. 236-242. https://doi.org/10.1086/430709
Campbell TB, Shulman NS, Johnson SC, Zolopa AR, Young RK, Bushman L et al. Antiviral activity of lamivudine in salvage therapy for multidrug-resistant HIV-1 infection. Clinical Infectious Diseases. 2005 Jul 15;41(2):236-242. https://doi.org/10.1086/430709
Campbell, Thomas B. ; Shulman, Nancy S. ; Johnson, Steven C. ; Zolopa, Andrew R. ; Young, Russell K. ; Bushman, Lane ; Fletcher, Courtney V. ; Lanier, E. Randall ; Merigan, Thomas C. ; Kuritzkes, Daniel R. / Antiviral activity of lamivudine in salvage therapy for multidrug-resistant HIV-1 infection. In: Clinical Infectious Diseases. 2005 ; Vol. 41, No. 2. pp. 236-242.
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abstract = "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.",
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