Antibodies to AIDS and heated factor VIII.
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Antibodies, Viral↗
Biomedical subjects
A Gringeri
Publications and source records attributed to A Gringeri.
Abnormalities of lymphocyte subsets are correlated with concentrate consumption in asymptomatic Italian hemophiliacs treated with concentrates made from American plasma.
Eighty-three symptom-free hemophiliacs were studied clinically, serologically and by in vitro tests for cellular immunity in a geographical area in which AIDS has not yet been encountered despite the exclusive use of concentrates manufactured from American sources of plasma. Some patients showed the following abnormalities: lymphopenia (4%), decreased T-helper/T-suppressor (Th/Ts) cell ratios (49%), or both abnormalities (2%). Low Th/Ts were mostly due to absolute or, less frequently, relative increases in Ts cells. The prevalence rates for these abnormalities were the same in patients treated with factor VIII or factor IX concentrates. There was an association between the higher Ts and lower Th cells counts and the low Th/Ts ratios and greater annual consumption of factor VIII and factor IX concentrates. These results support the view that protein load might be an important pathogenetic factor in lymphocyte abnormalities in symptom-free hemophiliacs.
Acquired Immunodeficiency Syndrome↗
Effect of halofenate on the serum binding of phenytoin.
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Blood Proteins↗
Lipid-based amphotericin B in the treatment of cryptococcosis.
Amphotericin B is the only antifungal drug which, despite its dose-limiting toxicity, can be given intravenously when an aggressive treatment is required. In an attempt to reduce the drug toxicity while retaining its therapeutic efficacy, new formulations of amphotericin B have been developed. The most promising have employed lipid vehicles such as liposomes. Three lipid-based amphotericin B formulations have been developed by pharmaceutical companies and are under active clinical investigation. Efficacy and safety data of these derivatives in animals and humans are reviewed, with particular concern to cryptococcal infection. The authors' experience with a small unilamellar liposomal amphotericin B formulation, AmBisome, in the primary therapy of cryptococcosis is reported. Nine AIDS patients affected with cryptococcosis, seven of whom had meningitis, were given AmBisome (3 mg/kg/day) for 3-6 weeks. Complete response was obtained in six patients, marked improvement in two, and failure in one. AmBisome was well tolerated and shortened the time to clinical and mycological response suggesting a further improvement in the management of cryptococcosis in AIDS patients.
AIDS-Related Opportunistic Infections↗
High-purity factor VIII concentrates produced without using monoclonal antibodies.
Manufacturers are attempting to increase the purity of FVIII concentrates. A strategy pursued by some is that of including a purification step (gel filtration, ion-exchange or affinity chromatography) that yields concentrates with an intermediate or final specific activity of 35 to 250 IU FVIII/mg of protein. The specific activity of the final product may be lower because serum albumin is added to some concentrates to stabilize FVIII. In hemophiliacs treated with these concentrates, FVIII recovery and half-life are at least as good as those for less pure concentrates. In patients with von Willebrand disease, these concentrates increase plasma levels of FVIII, but their capacity to normalize the bleeding time is not well established. The hypothesis that their reduced alloantigen load might slow the progression of human immunodeficiency virus (HIV) infection is still not validated, but a few prospective studies are now attempting to address this issue. All the concentrates undergo virucidal procedures based on pasteurization or treatment with solvent/detergent. It is well established that these virucidal methods and donor screening avoid HIV transmission. A recent large study has shown that a pasteurized concentrate carries a low risk of transmitting viral hepatitis. The assessment of safety from hepatitis of concentrates treated with solvent/detergent is based on favorable preliminary results.
Acquired Immunodeficiency Syndrome↗
National survey of human immunodeficiency virus infection in Italian hemophiliacs: 1983-1987. The Medical-Scientific Committee of the Fondazione dell'Emofilia.
Since 1983, the Medical-Scientific Committee of the Fondazione dell'Emofilia has carried out annual national surveys of patients with hemophilia and other congenital bleeding disorders to evaluate the prevalence and characteristics of human immunodeficiency virus (HIV) infection and related diseases. Clinical syndromes related to HIV infection were already present in a number of Italian hemophiliacs in 1983, but the first cases of acquired immunodeficiency syndrome (AIDS) only occurred in 1984. Subsequently, AIDS cases roughly doubled each year to reach the number of 57 in 1987. In this year, 637 of 2,792 patients (23%) were found to be anti-HIV-positive. The highest prevalence of seropositivity was found in hemophilia B patients (138 of 313, 44%), followed by hemophilia A (476 of 1,658, 29%), von Willebrand's disease (23 of 650, 4%) and other congenital bleeding disorders (2 of 171, 1%). Only 3 cases of seroconversions were observed since 1986, following the nationwide adoption of heat-treated concentrates. The differences in the prevalence of HIV infection between hemophiliacs from Italy and other European countries are discussed.
Acquired Immunodeficiency Syndrome↗
The use of recombinant factor VIII in the management of hemophilia.
Recombinant factor VIII is currently in the late stages of clinical trials. The available studies indicate that the product is safe and well-tolerated, and appears to be free of virus diseases such as HIV and hepatitis infections. Based on these early studies, recombinant coagulation factors appear to have enormous promise and potential for transfusion medicine. The synthesis of large quantities of safe material may lead to the development of techniques for daily administration of factor VIII aimed at the prevention of joint and soft tissue bleedings. There is also the promise of decreased costs, as techniques for the efficient synthesis of recombinant proteins are refined further.
Acquired Immunodeficiency Syndrome↗
Anti-LAV/HTLV-III antibodies in groups of individuals at high risk for infection in Italy.
We have studied anti-LAV/HTLV-III antibody prevalence in individuals at high risk for infection, such as intravenous drug addicts, hemophiliacs and homosexual men. Among intravenous drug addicts, LAV/HTLV-III infection was first recognized in 1981 and positive serum reactions for anti-LAV/HTLV-III antibody rose in successive years to 53%. Anti-LAV/HTLV-III antibody prevalence was 13.5% in the group of homosexual men, while in hemophiliacs treated with commercial concentrates it was 37% in 1984 and had increased to 45% in 1985. There was a significant correlation between antibody status and concentrate consumption in these patients. Results of studies of anti-LAV/HTLV-III antibody patterns with the Western blot technique suggest that antibodies against core proteins (mainly p25 and p18) and the envelope protein gp40 are always present in asymptomatic individuals and in patients with the lymphadenopathy syndrome, but usually not in patients with full-blown AIDS. These last patients have typical positive reactions only against the envelope proteins gp110 and gp40.
Acquired Immunodeficiency Syndrome↗
Antibodies to the HIV-1 Tat protein correlated with nonprogression to AIDS: a rationale for the use of Tat toxoid as an HIV-1 vaccine.
OBJECTIVES: To investigate which immune parameters, such as antibodies against HIV-1 specificities, or viral parameters, such as p24 antigenemia, are predictive of disease progression. STUDY DESIGN: We performed studies on serum collected from individuals exhibiting two extremes of disease evolution--67 fast progressors (FP) and 182 nonprogressors (NP)--at their enrollment. After a 1- to 2-year clinical follow-up of 104 nonprogressors after their enrollment, we could determine the best serologic predictors for disease progression. METHODS: We investigated levels of antibodies to tetanus toxoid and to HIV antigens including Env, Gag, Nef, and Tat proteins, as well as p24 antigenemia, viremia, CD4 cell count, and interferon-alpha (IFN-alpha) titers in FPs and NPs, and we correlated these data with clinical and biologic signs of progression. RESULTS: p24 Antigenemia, a marker of viral replication, and anti-Tat antibodies were highly and inversely correlated in both groups (P < .001). Furthermore, anti-p24 antibodies and low serum IFN-alpha levels were correlated to the NP versus the FP cohort. Finally, among NPs, only antibodies to Tat and not to the other HIV specificities (Env, Nef, Gag) were significantly predictive of clinical stability during their follow-up. CONCLUSION: Antibodies toward HIV-1 Tat, which are inversely correlated to p24 antigenemia, appear as a critical marker for a lack of disease progression. This study strongly suggests that rising anti-Tat antibodies through active immunization may be beneficial in AIDS vaccine development to control viral replication.
AIDS Vaccines↗
Safety and immunogenicity of HIV-1 Tat toxoid in immunocompromised HIV-1-infected patients.
OBJECTIVES: To antagonize the deleterious effects of the HIV-1 toxin extracellular Tat on uninfected immune cells, we developed a new strategy of anti-HIV-1 vaccine using an inactivated but immunogenic Tat (Tat toxoid). Tat toxoid has been assayed for safety and immunogenicity in seropositive patients. METHOD: The phase I vaccine clinical trial testing Tat toxoid preparation in Seppic Isa 51 oil adjuvant was performed on 14 HIV-1-infected asymptomatic although biologically immunocompromised individuals (500-200 CD4+ cells/mm3). RESULTS: Following as many as 8 injections, no clinical defects were observed. All patients exhibited an antibody (Ab) response to Tat, and some had cell-mediated immunity (CMI) as evaluated by skin test in vivo and T-cell proliferation in vitro. CONCLUSION: These results provide initial evidence of safety and potency of Tat toxoid vaccination in HIV-1-infected individuals.
AIDS Vaccines↗
[HIV-related thrombocytopenias].
Thrombocytopenia is a relatively frequent hematological complication in patients infected with the human immunodeficiency virus type 1. Occurring in all risk groups (homosexuals, intravenous drug addicts, hemophiliacs, heterosexuals) this complication has an overall prevalence varying between 5 and 15%. Only a relatively small proportion of patients have severe thrombocytopenia (6 to 24%), and life-endangering bleeding symptoms are not frequent. Accordingly, aggressive treatment is seldom indicated. Corticosteroids should be avoided because they may further compromise the deteriorated immune system of these patients. Splenectomy is efficacious as in patients with non-human immunodeficiency virus related immune thrombocytopenic purpura and infectious complications are not a prominent problem following the operation. Antiretroviral treatment with zidovudine and/or highly active protease inhibitors increases platelet count, but the control of thrombocytopenia is often transient when these drugs are stopped. Other treatments such as alpha-interferon and thrombopoietin require further experiences. On the whole, thrombocytopenia is generally a relatively mild complication of the human immunodeficiency virus infection and aggressive treatment is often unwarranted.
Anti-HIV Agents↗