Brian Wigdahl

By Lorena Loarca, Neil Sullivan, Vanessa Pirrone and Brian Wigdahl

Two human retroviruses, identified as the human T-cell leukemia virus type 1 (HTLV-1) and human immunodeficiency virus type 1 (HIV-1), have been shown to affect millions of people worldwide. In the context of coinfection, the impact of their interactions with respect to HTLV-1-induced adult T-cell leukemia and neurologic disease as well as HIV-1 disease progression has been an understudied area of investigation. HTLV-1/HIV-1 coinfections occur frequently, particularly in large metropolitan areas of the Americas, Africa, Europe, and Japan. The retroviruses HTLV-1 and HIV-1 share some similarities with regard to their genetic structure, general mechanisms of replication, modes of transmission, and cellular tropism; however, there are also significant differences in the details of these properties as well, and they also differ significantly with respect to the etiology of their pathogenic and disease outcomes. Both viruses impair the host immune system with HIV-1 demonstrated to cause the hallmark lethal disease known as the acquired immune deficiency syndrome (AIDS), while HTLV-1 infection has been shown to cause several different forms of T-cell leukemia. In addition, both viruses have also been shown to cause a spectrum of neurologic disorders with HIV-1 shown to cause an array of neurologic syndromes referred to as HIV-1-associated neurologic disorders or HAND, while HTLV-1 has been shown to be the etiologic agent of HTLV-1-associated myelopathy/tropical spastic paraparesis or HAM/TSP. The natural history of the coinfection, however, is different from that observed in monoinfections. Several studies have demonstrated utilizing a number of in vitro models of HTLV-1/HIV-1 coinfection that the two viruses interact in a manner that results in enhanced expression of both viral genomes. Nevertheless, there remains unresolved controversy regarding the overall impact of each virus on progression of disease caused by both viruses during the course of coinfection. Although combination antiretroviral therapy has been shown to work very effectively with respect to maintaining HIV-1 viral loads in the undetectable range, these therapeutic strategies exhibit no benefit for HTLV-1-infected individuals, unless administered immediately after exposure. Furthermore, the treatment options for HTLV-1/HIV-1-coinfected patients are very limited. In recent years, allogeneic stem cell transplantation (alloSCT) has been used for the treatment of leukemia. In this regard, the case of a leukemic patient positive for HIV-1 who was cured of their HIV-1 infection while treated with alloSCT for acute myeloid leukemia has also been examined with regard to impact on HIV-1 disease.

Part of the book: Leukemias

By Lorena Loarca, Joseph A. Fraietta, Vanessa Pirrone, Zsofia Szep and Brian Wigdahl

Human immunodeficiency virus type 1 (HIV-1) infection confers an increased risk for the development of many cancers. Although the incidences of acquired immunodeficiency syndrome (AIDS)-defining malignancies have declined since the advent of antiretroviral therapy (ART), a number of non-AIDS–defining cancers appear more common in HIV-1–infected individuals relative to the general population. ART-treated HIV-1–infected subjects are also aging, leading to an increased cancer burden in these populations. However, longevity alone is not sufficient to explain these epidemiologic trends. A causative link between HIV-1–induced immune suppression and elevated cancer risk is well defined in certain malignancies; however, the direct role of HIV-1 replication products in oncogenesis remains unclear. Nevertheless, it is evident that cooperation between HIV-1 and co-infecting viruses in targeting immune compartments as well as nonimmune microenvironments can regulate both the development and progression of cancer. Treating cancer in HIV-1–infected patients remains challenging due to drug interactions, compounded side effects and intensified immunosuppression from chemotherapy and/or radiation. While survival of HIV-1–infected patients with certain cancers now rivals that of their uninfected counterparts, a better understanding of HIV-1–induced oncogenesis, viral mechanisms of immune perturbation, nonimmune microenvironmental abnormalities and outcomes of therapy will provide the basis for better diagnosis and management of cancer.

Part of the book: HIV/AIDS