Controlling Viral Replication in HIV-1-Infected Patients
Controlling Viral Replication in HIV-1-Infected Patients
Restoring and preserving immune function is a key component to successfully managing HIV-1 disease. Phase II/III studies have evaluated the safety and immunologic effects of immune-based therapies, including granulocyte-macrophage colony-stimulating factor, interleukin-2, and an inactivated HIV-1 immunogen, as adjuncts to antiretroviral therapy. Addition of each of these immune-based therapies to a background antiretroviral regimen enhanced, to varying degrees, immunologic function and suppression of viral replication in HIV-1-infected patients, suggesting a potential role for immune-based therapies in the treatment of HIV-1 disease. Further studies are needed to better characterize specific immunologic and virologic effects in different patient populations and to determine their impact on clinical outcomes.
Human immunodeficiency virus type 1 (HIV-1) infection is characterized by progressive immune system dysfunction that results in profound immunosuppression. Disease progression is associated with the development of potentially lethal opportunistic infections, malignancies, progressive neurologic disease, and hematopoietic abnormalities. Despite extensive prevention programs, the number of persons living with HIV/AIDS in the United States continues to increase; AIDS is a leading cause of death in persons aged 25 to 44 years. Introduction of HAART consisting of at least 3 drugs has substantially reduced the opportunistic infections, hospitalizations, and mortality associated with advanced HIV-1 infection.
Unfortunately, HAART has little effect on the viral reservoir of latently infected CD4 lymphocytes established early in HIV-1 infection. As a result, a large proportion of patients experience a rebound in HIV-1 viral load and further decline in CD4 cell counts even after receiving a second protease inhibitor (PI)-based HAART regimen. The long-term benefit of HAART is also limited by the emergence of PI resistant strains of HIV-1 and the toxicity associated with these regimens. In addition, the ability of HAART to improve immune responses against HIV-1 and opportunistic pathogens is variable and modest at best.
More recent strategies to improve the long-term treatment of HIV-1 infection have focused on enhancing or restoring functional cell-mediated immune (CMI) responses to HIV-1 infection. Several immune-based therapeutic strategies, including cytokine therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF) (sargramostim) or interleukin-2 (IL-2) (aldesleukin) and vaccine therapy with an inactivated HIV-1 immunogen (Remune), have undergone clinical evaluation as adjuncts to stable antiretroviral therapy (Table 1). Encouraging results from phase II/III studies indicate that some immune-based therapies can increase CD4 cell counts, enhance CMI response, and/or potentially decrease viral load or maintain suppression of viral replication. Research is ongoing to better characterize specific immunologic and virologic effects of these therapies and to determine their potential impact on clinical outcomes.
Restoring and preserving immune function is a key component to successfully managing HIV-1 disease. Phase II/III studies have evaluated the safety and immunologic effects of immune-based therapies, including granulocyte-macrophage colony-stimulating factor, interleukin-2, and an inactivated HIV-1 immunogen, as adjuncts to antiretroviral therapy. Addition of each of these immune-based therapies to a background antiretroviral regimen enhanced, to varying degrees, immunologic function and suppression of viral replication in HIV-1-infected patients, suggesting a potential role for immune-based therapies in the treatment of HIV-1 disease. Further studies are needed to better characterize specific immunologic and virologic effects in different patient populations and to determine their impact on clinical outcomes.
Human immunodeficiency virus type 1 (HIV-1) infection is characterized by progressive immune system dysfunction that results in profound immunosuppression. Disease progression is associated with the development of potentially lethal opportunistic infections, malignancies, progressive neurologic disease, and hematopoietic abnormalities. Despite extensive prevention programs, the number of persons living with HIV/AIDS in the United States continues to increase; AIDS is a leading cause of death in persons aged 25 to 44 years. Introduction of HAART consisting of at least 3 drugs has substantially reduced the opportunistic infections, hospitalizations, and mortality associated with advanced HIV-1 infection.
Unfortunately, HAART has little effect on the viral reservoir of latently infected CD4 lymphocytes established early in HIV-1 infection. As a result, a large proportion of patients experience a rebound in HIV-1 viral load and further decline in CD4 cell counts even after receiving a second protease inhibitor (PI)-based HAART regimen. The long-term benefit of HAART is also limited by the emergence of PI resistant strains of HIV-1 and the toxicity associated with these regimens. In addition, the ability of HAART to improve immune responses against HIV-1 and opportunistic pathogens is variable and modest at best.
More recent strategies to improve the long-term treatment of HIV-1 infection have focused on enhancing or restoring functional cell-mediated immune (CMI) responses to HIV-1 infection. Several immune-based therapeutic strategies, including cytokine therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF) (sargramostim) or interleukin-2 (IL-2) (aldesleukin) and vaccine therapy with an inactivated HIV-1 immunogen (Remune), have undergone clinical evaluation as adjuncts to stable antiretroviral therapy (Table 1). Encouraging results from phase II/III studies indicate that some immune-based therapies can increase CD4 cell counts, enhance CMI response, and/or potentially decrease viral load or maintain suppression of viral replication. Research is ongoing to better characterize specific immunologic and virologic effects of these therapies and to determine their potential impact on clinical outcomes.