Cellular factors involved in the induction of resistance of HIV to antiretroviral agents

Long-term treatment of HIV-1 infected patients with antiretroviral agents m ay result in failure of therapy due to the emergence of resistant virus mut ants with decreased susceptibility to the therapeutic agents. Several autho rs have asked whether cellular factors, other than viral mutation may contr ibute to the declining efficiency of chemotherapy including nucleoside anal ogues and protease inhibitors (PI). Prolonged treatment with AZT may induce a defect of thymidine kinase activity in vitro and in vivo. Long-term trea tment with other nucleoside analogues, such as d4T and 3TC, is also able to induce in host cells, a decreased sensitivity to the antiviral activity of these compounds. It is suggested that antiviral activity of PI could be mo dified by the expression of a protein P-gp that has been demonstrated to be able to bind PI and is involved in extrusion of anticancer agents. (C) 200 0 Elsevier Science B.V. and International Society of Chzmotherapy. All righ ts reserved.