Viro-immunological dynamics in HIV-1-infected subjects receiving once-a-week emtricitabine to delay treatment change after failure

A pilot randomised trial

Alessandro Soria, Anna Danise, Laura Galli, Simon Tiberi, Elena Seminari, Francesca Cossarini, Alba Bigoloni, Simone Marcotullio, Adriano Lazzarin, Antonella Castagna

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: In HIV-1-infected patients harbouring the M184V mutation (M184V), lamivudine monotherapy leads to a smaller decrease in CD4 percentages (CD4%) than treatment interruption, possibly due to the reduced fitness of the mutated virus. Objective: We assessed whether a minimal dose of a cytidine analogue that is theoretically sufficient to maintain M184V (one emtricitabine tablet once-weekly) may be as effective. Study design: In a proof-of-concept, randomised clinical trial, HIV-1-infected patients with CD4 cells >400/mm3, failing on lamivudine- or emtricitabine-containing combination antiretroviral therapy (cART), received emtricitabine once-a-week (A), or emtricitabine once-a-day (B), or lamivudine once-a-day (C). The primary endpoint was the proportion of subjects without a 12-week loss in CD4%. The patients resumed cART after 24 weeks or in the case of CD4 cells 3. Results: The 38 enrolled patients had similar baseline characteristics across groups. The primary endpoint was reached by 5/13 patients (38.5%) in arm A, 3/13 (23.1%) in arm B, and 3/12 (25%) in arm C (P = 0.644), and respectively 4/13 (30.8%), 4/13 (30.8%) and 5/12 (41.7%) had to resume cART within 24 weeks (P = 0.805). The immunological changes over 24 weeks were similar in the three groups, but there was a higher median viral rebound in once-weekly treatment recipients (A) than in once-daily (B + C): 0.97 versus 0.52 log10 copies/ml (P = 0.033). M184V was maintained in all the participants. Conclusions: Once-weekly emtricitabine led to a higher viral rebound than once-daily monotherapy, but similar immunological changes, thus suggesting a role of M184V in slowing the decrease in CD4% in treatment failing subjects.

Original languageEnglish
Pages (from-to)253-257
Number of pages5
JournalJournal of Clinical Virology
Volume47
Issue number3
DOIs
Publication statusPublished - Mar 2010

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HIV-1
Lamivudine
Therapeutics
Cytidine
Tablets
Emtricitabine
Randomized Controlled Trials
Viruses
Mutation

Keywords

  • Emtricitabine
  • Lamivudine
  • M184V mutation
  • Randomised clinical trial
  • Salvage regimen
  • Virological failure

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Viro-immunological dynamics in HIV-1-infected subjects receiving once-a-week emtricitabine to delay treatment change after failure : A pilot randomised trial. / Soria, Alessandro; Danise, Anna; Galli, Laura; Tiberi, Simon; Seminari, Elena; Cossarini, Francesca; Bigoloni, Alba; Marcotullio, Simone; Lazzarin, Adriano; Castagna, Antonella.

In: Journal of Clinical Virology, Vol. 47, No. 3, 03.2010, p. 253-257.

Research output: Contribution to journalArticle

Soria, Alessandro ; Danise, Anna ; Galli, Laura ; Tiberi, Simon ; Seminari, Elena ; Cossarini, Francesca ; Bigoloni, Alba ; Marcotullio, Simone ; Lazzarin, Adriano ; Castagna, Antonella. / Viro-immunological dynamics in HIV-1-infected subjects receiving once-a-week emtricitabine to delay treatment change after failure : A pilot randomised trial. In: Journal of Clinical Virology. 2010 ; Vol. 47, No. 3. pp. 253-257.
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abstract = "Background: In HIV-1-infected patients harbouring the M184V mutation (M184V), lamivudine monotherapy leads to a smaller decrease in CD4 percentages (CD4{\%}) than treatment interruption, possibly due to the reduced fitness of the mutated virus. Objective: We assessed whether a minimal dose of a cytidine analogue that is theoretically sufficient to maintain M184V (one emtricitabine tablet once-weekly) may be as effective. Study design: In a proof-of-concept, randomised clinical trial, HIV-1-infected patients with CD4 cells >400/mm3, failing on lamivudine- or emtricitabine-containing combination antiretroviral therapy (cART), received emtricitabine once-a-week (A), or emtricitabine once-a-day (B), or lamivudine once-a-day (C). The primary endpoint was the proportion of subjects without a 12-week loss in CD4{\%}. The patients resumed cART after 24 weeks or in the case of CD4 cells 3. Results: The 38 enrolled patients had similar baseline characteristics across groups. The primary endpoint was reached by 5/13 patients (38.5{\%}) in arm A, 3/13 (23.1{\%}) in arm B, and 3/12 (25{\%}) in arm C (P = 0.644), and respectively 4/13 (30.8{\%}), 4/13 (30.8{\%}) and 5/12 (41.7{\%}) had to resume cART within 24 weeks (P = 0.805). The immunological changes over 24 weeks were similar in the three groups, but there was a higher median viral rebound in once-weekly treatment recipients (A) than in once-daily (B + C): 0.97 versus 0.52 log10 copies/ml (P = 0.033). M184V was maintained in all the participants. Conclusions: Once-weekly emtricitabine led to a higher viral rebound than once-daily monotherapy, but similar immunological changes, thus suggesting a role of M184V in slowing the decrease in CD4{\%} in treatment failing subjects.",
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AU - Galli, Laura

AU - Tiberi, Simon

AU - Seminari, Elena

AU - Cossarini, Francesca

AU - Bigoloni, Alba

AU - Marcotullio, Simone

AU - Lazzarin, Adriano

AU - Castagna, Antonella

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N2 - Background: In HIV-1-infected patients harbouring the M184V mutation (M184V), lamivudine monotherapy leads to a smaller decrease in CD4 percentages (CD4%) than treatment interruption, possibly due to the reduced fitness of the mutated virus. Objective: We assessed whether a minimal dose of a cytidine analogue that is theoretically sufficient to maintain M184V (one emtricitabine tablet once-weekly) may be as effective. Study design: In a proof-of-concept, randomised clinical trial, HIV-1-infected patients with CD4 cells >400/mm3, failing on lamivudine- or emtricitabine-containing combination antiretroviral therapy (cART), received emtricitabine once-a-week (A), or emtricitabine once-a-day (B), or lamivudine once-a-day (C). The primary endpoint was the proportion of subjects without a 12-week loss in CD4%. The patients resumed cART after 24 weeks or in the case of CD4 cells 3. Results: The 38 enrolled patients had similar baseline characteristics across groups. The primary endpoint was reached by 5/13 patients (38.5%) in arm A, 3/13 (23.1%) in arm B, and 3/12 (25%) in arm C (P = 0.644), and respectively 4/13 (30.8%), 4/13 (30.8%) and 5/12 (41.7%) had to resume cART within 24 weeks (P = 0.805). The immunological changes over 24 weeks were similar in the three groups, but there was a higher median viral rebound in once-weekly treatment recipients (A) than in once-daily (B + C): 0.97 versus 0.52 log10 copies/ml (P = 0.033). M184V was maintained in all the participants. Conclusions: Once-weekly emtricitabine led to a higher viral rebound than once-daily monotherapy, but similar immunological changes, thus suggesting a role of M184V in slowing the decrease in CD4% in treatment failing subjects.

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