Service de virologie, GH Pitié-Salpêtrière, Université Pierre et Marie Curie, Paris
Pathways leading to resistance to entry inhibitors differ substantially from those causing resistance to other antiretrovirals, and therefore no cross-resistance is anticipated between entry inhibitors and other classes of antiretrovirals currently in use. Some mechanisms of resistance to entry inhibitors have been characterized or are under investigation. It has been shown that the main mechanism of resistance to enfuvirtide is the selection of mutations in a domain of 10 amino acids in gp41. For other entry inhibitors, multiple changes in different gp120 domains (V3, C2, C4 and V4) seem to be responsible for causing loss of susceptibility. Concerning CCR5 antagonists, it has been shown that co-receptor shift to CXCR4 use can be possible. Simultaneously to clinical development of these new antiretrovirals, further investigation of resistance pathways leading to resistance to entry inhibitors are warranted, in order to explore for example the degree of cross-resistance within this new class.