Search

Background: The demonstration of in vitro cardiolipin reactivity with 2 human immunodeficiency virus (HIV)-specific, broadly neutralizing antibodies (2F5 and 4E10) has prompted reevaluation of autoimmune manifestations in HIV infection., Methods: We evaluated autoantibodies, particularly anticardiolipin (aCL), in 67 untreated, asymptomatic, HIV-infected individuals with slow progression of HIV disease and their correlation with 2F5-, 4E10-, b12-, and 2G12-like antibodies directed against epitopes involved in broad neutralization, as well as their correlation with immune activation and virological and clinical indicators. Fifty individuals with chronic HIV infection and standard disease progression were control patients., Results: The majority of the study patients with slow progression of HIV disease were men (78%); their median age was 37 years, their median CD4+ cell count was 672 cells/mL, and their median plasma HIV load was 6200 copies/mL. The majority of the control patients were also men (76%), and most (62%) were receiving highly active antiretroviral therapy; their median age was 43 years, their median CD4+ cell count was 202 cells/mL, and their median plasma HIV load was 2265 copies/mL. aCL immunoglobulin G was detected at similar levels in 49% of patients with slow progression of HIV disease and in 58% of control patients. Viral load was positively associated with aCL in both groups (P < .001), independent of CD4+ cell counts. In patients with slow progression of HIV disease, aCL levels were also correlated with plasma HIV load and cell-associated DNA level (r = 0.486 and r = 0.516, respectively; P < .001), with the proportion of activated CD4+ cells, human leukocyte antigen-DR+ cells (r = 0.445; P = or < .001) but not activated CD8+ T cells, and with the level of B cell activation (quantified by soluble CD23; r = 0.354; P = .007). The level of aCL antibodies was associated with the level of antibodies to the membrane proximal region of gp41 (P = .003)., Conclusion: aCL is frequently detected in HIV-infected patients, regardless of disease stage, and is strongly linked with the level of viral replication, the level of CD4+ T and B cell activation, and the level of antibodies to the membrane proximal external region of gp41, independent of CD4+ cell deficiency.

Background: Strong T cell and antibody responses to human immunodeficiency virus (HIV), low virus production, and some genetic traits have been individually associated with nonprogression of HIV infection, but the best correlate with protection against disease progression remains unknown., Methods: We prospectively followed 66 untreated long-term nonprogressors and analyzed relationships between HIV-1-specific CD4 T helper (Th) 1 and CD8 T cell responses and HIV-1-specific antibodies, HIV-1 RNA and proviral DNA loads, host genes, and CD4 Th1 cell counts at entry into the study and 4 years later., Results: HIV-1 p24-specific CD4 Th1 cell proliferation, interferon (IFN)- gamma production, and IFN- gamma -producing cell frequencies at entry significantly and negatively correlated with HIV-1 RNA and proviral DNA loads and were independent of CD4 Th1 cell counts and host genes. HIV-1 Gag-specific IFN- gamma -producing CD8 T cell frequencies correlated with HIV-1 proviral DNA loads but not with RNA loads. Only high frequencies of HIV-1 p24-specific CD4 Th1 cells combined with HIV-1 gp41-specific IgG2 antibodies significantly predicted persistence of high CD4 Th1 cell counts., Conclusion: HIV-1-specific CD4 Th1 responses combined with IgG2 antibodies and IFN- gamma -producing CD4 Th1 cells are better predictors of long-term nonprogression than are virus parameters, host genes, or HIV-1-specific CD4 Th1 or CD8 T cell proliferation.

Multicentric Castleman disease (MCD) is a distinct type of lymphoproliferative disorder associated with inflammatory symptoms and interleukin 6 (IL-6) dysregulation. In the context of human immunodeficiency virus (HIV) infection, MCD is associated with Kaposi sarcoma-associated herpesvirus, also called human herpesvirus type 8 (KSHV/HHV8). Within a prospective cohort study on 60 HIV-infected patients with MCD, and a median follow-up period of 20 months, 14 patients developed KSHV/HHV8-associated non-Hodgkin lymphoma (NHL): 3 "classic" KSHV/HHV8(+) Epstein-Barr virus-positive (EBV(+)) primary effusion lymphoma (PEL), 5 KSHV/HHV8(+) EBV(-) visceral large cell NHL with a PEL-like phenotype, and 6 plasmablastic lymphoma/leukemia (3/3 KSHV/HHV8(+) EBV(-)). The NHL incidence observed in this cohort study (101/1000 patient-years) is about 15-fold what is expected in the general HIV(+) population. MCD-associated KSHV/HHV8(+) NHL fell into 2 groups, suggesting different pathogenesis. The plasmablastic NHL likely represents the expansion of plasmablastic microlymphoma from the MCD lesion and progression toward aggressive NHL. In contrast, the PEL and PEL-like NHL may implicate a different original infected cell whose growth is promoted by the cytokine-rich environment of the MCD lesions.

Study Objective: To determine whether zidovudine is effective in increasing the platelet count in patients with thrombocytopenic purpura related to human immunodeficiency virus (HIV) infection.Design: Nonrandomized controlled trial with two consecutive regimens.Setting: Immunopathology and hematology clinics at two general hospitals.Patients: Consecutive sample of 34 patients infected with HIV who had thrombocytopenic purpura (platelets less than 50 x 10(9)/L) without visceral bleeding. Twenty-nine patients completed the study; one patient was removed because of drug toxicity.Interventions: Zidovudine for 12 weeks, 250 mg every 6 hours orally in 10 patients; and 500 mg every 8 hours orally in 24 patients.Measurements and Main Results: Three of ten patients receiving 250 mg every 6 hours and 12 of 24 patients receiving 500 mg every 8 hours had a persistent increase in their platelet counts. In both groups the mean value of the platelet count increased significantly by week 12; from 28 x 10(9)/L +/- 12 (SD) to 57 x 10(9)/L +/- 36 in the first group and from 20 x 10(9)/L +/- 13 to 77 x 10(9)/L +/- 42 in the second group (P less than 0.05 and P less than 0.01, respectively).Conclusions: Zidovudine is effective on platelet counts in some patients with HIV-related thrombocytopenia. These results suggest that HIV itself may play a direct or indirect role in the pathogenesis of this disorder. [ABSTRACT FROM AUTHOR]