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Drug resistance mutations and the cellular immune response: a valuable synergy for the development of novel immune therapies

Chomont, Nicolasa,b,c,*; Trautmann, Lydiea,b,c,*; Routy, Jean-Pierrec,d; Sékaly, Rafick-Pierrea,b,c,e

Current Opinion in HIV and AIDS: March 2007 - Volume 2 - Issue 2 - p 116–122
doi: 10.1097/COH.0b013e3280287a4d
Antiretroviral drug resistance: Basic science
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Purpose of review The escape of HIV-1 is a cardinal feature of the virus and a major hindrance to the development of effective therapeutic strategies. In highly active antiretroviral therapy-treated patients, the virus is subjected to selective pressures from cellular immune response directed against the viral proteome and antiretroviral treatment targetting a few genes of the HIV-1 genome. This review will focus on the relationship between these two pressures and its potential advantage in the development of novel immune therapies.

Recent findings Recent studies have investigated the conflicting selective forces between viral fitness and escape to immunological and therapeutic pressures in natural HIV infection and the SIV model. Simultaneous pressures driven by cytotoxic T lymphocytes and highly active antiretroviral therapy could potentially reduce viral fitness, leading to better control of the viral load. Two studies have described a potential therapeutic vaccine strategy against viral escape mutant epitopes from reverse transcriptase inhibitors.

Summary The emergence of multidrug-resistant viruses is associated with enhanced T-cell-mediated immune response as a possible consequence of reduced viral fitness. Amino acid substitutions generate potential cytotoxic T-lymphocyte epitopes that may elicit new reactivities against mutated viruses. Both could significantly enhance the immune response through direct and indirect mechanisms.

aLaboratoire d'Immunologie, Centre de Recherche CHUM Saint-Luc

bLaboratoire d'Immunologie, Département de Microbiologie et d'Immunologie, Université de Montréal

cINSERM U743, CR-CHUM, Université de Montréal

dImmunodeficiency Service and Division of Haematology, Royal Victoria Hospital, McGill University Health Centre, McGill University, Montréal, Québec, Canada

eDepartment of Microbiology and Immunology, McGill University

*Co-first authors.

Correspondence to Rafick-Pierre Sékaly, Laboratoire d'Immunologie, Centre de Recherche CHUM Saint-Luc, Montréal, Québec, Canada E-mail: rafick-pierre.sekaly@umontreal.ca

© 2007 Lippincott Williams & Wilkins, Inc.