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


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.
Division of Infectious Diseases, Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA. Thomas.Campbell@uchsc.edu
Thomas B
TB
Campbell
Nancy S
NS
Shulman
Steven C
SC
Johnson
Andrew R
AR
Zolopa
Russell K
RK
Young
Lane
L
Bushman
Courtney V
CV
Fletcher
E Randall
ER
Lanier
Thomas C
TC
Merigan
Daniel R
DR
Kuritzkes
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology; D018791:CD4 Lymphocyte Count; D024921:Drug Resistance, Multiple, Viral; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012367:RNA, Viral / Q000097:blood; D016879:Salvage Therapy; D019562:Viral Load
D019380:Anti-HIV Agents; D012367:RNA, Viral; D019259:Lamivudine