Cellular Factors Involved in the Induction of Resistance of HIV to Antiretroviral Agents

Long-term treatment of HIV-1 infected patients with antiretroviral agents may result in failure of therapy due to the emergence of resistant virus mutants with decreased susceptibility to the therapeutic agents. Several authors have asked whether cellular factors, other than viral mutation may contribute to the declining efficiency of chemotherapy including nucleoside analogues and protease inhibitors (PI). Prolonged treatment with AZT may induce a defect of thymidine kinase activity in vitro and in vivo. Long-term treatment 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 modified 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.