Article

Antiviral activity of lamivudine in salvage therapy for multidrug-resistant HIV-1 infection

Harvard University, Cambridge, Massachusetts, United States
Clinical Infectious Diseases (Impact Factor: 9.42). 08/2005; 41(2):236-42. DOI: 10.1086/430709
Source: PubMed

ABSTRACT 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.
Selective lamivudine withdrawal was studied in 6 subjects who had incomplete viral suppression during antiretroviral treatment for multidrug-resistant HIV-1 infection.
Plasma levels of HIV-1 RNA increased to 0.5 log(10) 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 log(10) 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.
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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    • "lower in the lamivudine monotherapy-group [Castagna et al., 2006]. The possible explanations for this finding include reduced HIV-1 fitness and residual antiviral activity of lamivudine despite the presence of the 184V mutation [Campbell et al., 2005; Deeks et al., 2005]. The aim of this study was to investigate the mechanisms underlying the virological and immunological changes occurring in patients undergoing treatment interruption or lamivudine monotherapy after treatment failure in the presence of the 184V mutation. "
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