HIV fitness and resistance as covariates associated with the appearance of mutations under antiretroviral treatment

Carlo Federico Perno, Alessandra Cenci, Cristina Piro, Roberta D'Arrigo, Luisa Marcon, Francesca Ceccherini-Silberstein, Franca Ascoli Marchetti, Raffaele Caliò, Andrea Antinori

Research output: Contribution to journalArticlepeer-review

Abstract

The ability of human immunodeficiency virus (HIV) strains to replicate in human target cells represents a major driving force of the progression of the disease. Despite antiretroviral treatment, HIV overcomes drug pressure by adding new (compensatory) mutations, appearing in a specific and sequential order, that modulate its replication capacity and favour viral escape. In the case of M184V (a mutation involving the catalytic site of HIV reverse transcriptase), no pathways of viral escape have been defined so far; it is thus conceivable that the mutated virus maintains a relatively low replicative capacity. At the time of interruption of specific viral pressure (lamivudine in the case of M184V), wild-type virus easily overgrows mutated strains. A deep molecular analysis (90 clones) conducted on proviral DNA of lymphocytes demonstrates that M184V strains are no longer detected in plasma and proviral DNA shortly after interruption of therapeutic regimens including lamivudine (even if a new therapeutic regimen has been started). This supports the concept that the low fitness of M184V strains is not easily compensated by additional mutations. Taken together, the results suggest that the assessment of viral fitness, either direct (through biological methods) or indirect (through the identification of specific mutations that affect the replicative capacity), may provide substantial advancements in the definition of the long-term efficacy of antiretroviral therapy.

Original languageEnglish
Pages (from-to)37-40
Number of pages4
JournalScandinavian Journal of Infectious Diseases, Supplement
Issue number106
Publication statusPublished - Dec 2003

ASJC Scopus subject areas

  • Immunology
  • Microbiology (medical)

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