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


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/microL, 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/microL (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.
Division of Infectious Diseases, University Hospital of Zurich, Zurich, Switzerland. Milos.Opravil@zim.ch
Milos
M
Opravil
Thomas
T
Klimkait
Severine
S
Louvel
Eva
E
Wolf
Manuel
M
Battegay
Christoph A
CA
Fux
Enos
E
Bernasconi
Martin
M
Vogel
Roberto
R
Speck
Rainer
R
Weber
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D011446:Prospective Studies; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D019259:Lamivudine; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase