thioguanine-anhydrous and HIV-Infections

In this review we will discuss the recent findings in HIV-associated multicentric Castleman disease. On the basis of current knowledge on pathophysiology, we will illustrate different therapeutic approaches and try to provide guidelines at least for the initial care of the disease.. On the basis of pathological and virological data, pathophysiology appears to conjugate both proliferation of human herpesvirus (HHV-8) infected plasmablasts and replication of HHV-8. Therefore, recent therapies have targeted the infected cells using chemotherapy or rituximab, an anti-CD20 monoclonal antibody or both, and the virus replication by using valganciclovir, a potent antiviral drug usually used against cytomegalovirus.. Etoposide is the most effective first-line therapy for active multicentric Castleman disease. Rituximab can be used after an initial control of the attack and provides a 1-yearremission rate above 70%. Exacerbation of Kaposi sarcoma lesions, observed in half of the patients with previous Kaposi sarcoma lesions, may represent a limitation.Valganciclovir effectively suppresses HHV-8 replication both in vitro and in vivo, and reduction in HHV-8 viremia associated with clinical improvement has been suggested in short series of patients with multicentric Castleman disease treated with valganciclovir.

Topics: Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Asparaginase; Castleman Disease; Clinical Trials as Topic; Cytarabine; Daunorubicin; Etoposide; Ganciclovir; Herpesviridae Infections; Herpesvirus 8, Human; HIV Infections; Humans; Lymph Nodes; Rituximab; Thioguanine; Valganciclovir; Virus Replication

Topics: Adult; Anti-HIV Agents; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Cytarabine; Daunorubicin; Drug Therapy, Combination; HIV Infections; Humans; Leukemia, Myeloid, Acute; Male; Thioguanine; Zidovudine

To evaluate the types and mechanisms of stroke in a large population of HIV-infected patients.. We reviewed records of consecutive HIV-infected patients with acute stroke admitted to a large metropolitan hospital between 1996 and 2004. Stroke mechanism was defined by consensus between two cerebrovascular neurologists using TOAST classification.. A total of 82 patients were included, 77 with ischemic stroke and 5 with intracerebral hemorrhage. Mean age was 42 years and 89% were African American. Previous diagnosis of HIV infection was documented in 91% and AIDS diagnosis in 80%. Mean CD4 count was 113 cells/mm(3) and 85% had CD4 count <200 cells/mm(3). A total of 61% of patients had received combination antiretroviral treatment (CART). The mechanism of ischemic stroke was large artery atherosclerosis in 12%, cardiac embolism in 18%, small vessel occlusion in 18%, other determined etiology in 23%, and undetermined in 29% (including 19% with incomplete evaluation). Vasculitis was deemed responsible for the stroke in 10 patients (13%) and hypercoagulability in 7 (9%). Protein S deficiency was noted in 10/22 (45%) and anticardiolipin antibodies in 9/31 (29%) tested patients. When comparing patients with large or small vessel disease (atherothrombotic strokes) vs the rest of the population, there were no differences in exposure to CART or CD4 count, but patients with non-atherothrombotic strokes were younger (p = 0.04). Recent cocaine exposure was less common among patients with atherothrombotic strokes (p = 0.02). Strokes were fatal or severely disabling in 35% of cases.. Stroke mechanisms are variable in HIV-infected patients, with a relatively high incidence of vasculitis and hypercoagulability. In our population of severely immunodepressed patients, exposure to combination antiretroviral treatment did not significantly influence the mechanism of stroke.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Brain Ischemia; Cardiolipins; CD4 Lymphocyte Count; Cerebral Hemorrhage; Child; Child, Preschool; Cocaine-Related Disorders; Comorbidity; Cytarabine; Daunorubicin; Female; HIV Infections; Humans; Incidence; Intracranial Arteriosclerosis; Intracranial Embolism; Male; Middle Aged; Protein S Deficiency; Retrospective Studies; Stroke; Thioguanine; Thrombophilia; Vasculitis

Although highly active antiretroviral therapy against human immunodeficiency virus (HIV) type 1 reduces the mortality of persons with acquired immunodeficiency syndrome, it does not eliminate HIV reservoirs. In this study, which used a 6-thioguanine (6-TG) resistant clone (4C6) of the MT-2 cell line as a model, the combination of 6-TG with both reverse-transcriptase (RT) inhibitor and protease inhibitor or 6-TG with a protease inhibitor alone completely eradicated HIV-1-carrying cells from the culture and protected uninfected 4C6 cells from HIV-1 infection. The combination of 6-TG and a RT inhibitor, azidothymidine, provided partial protection. Protection was extended to human peripheral blood mononuclear cells. These results suggest that adding a cytotoxic drug in combination antiviral chemotherapy may reduce the establishment of virus reservoirs and prevent virus spread. The clinical value of this and similar strategies should be further evaluated in HIV-infected patients.

Topics: Cells, Cultured; Drug Therapy, Combination; HIV Core Protein p24; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Pilot Projects; Reverse Transcriptase Inhibitors; Thioguanine