Granulocyte colony-stimulating factor treatment in AIDS patients

Summary Frequent complications of human immunodeficiency virus infection are hematopoietic failure and poor tolerance of myelosuppressive drugs. Reasons for neutropenia resulting from hematopoietic failure are infection of the bone marrow and hematotoxicity of treatment with zidovudine, ganciclovir, sulfonamides, and interferons. Moreover, tumor necrosis factor-, transforming growth factor- and interferon- have been shown to suppress proliferation of bone marrow cells. Both granulocyte (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) increase neutrophil counts and ameliorate phagocytic and bactericidic function of neutrophils. We report eight cases of AIDS patients with serious infections and neutropenia (< 750 cells/l), who were treated concomitantly with recombinant human G-CSF (3–4 g subcutaneously per kilogram body weight daily). G-CSF treatment was well tolerated in all patients and showed no side effects or disturbances of other lineages than neutrophils. Life-threatening bacterial infections were treated successfully by stimulating the neutrophil immune system. This therapy shortened the duration of subsequent treatment with antibiotics. Since human immunodeficiency virus infects CD4-positive monocytes and macrophages, which are stimulated by GM-CSF, G-CSF seems to be the cytokine of choice, if stimulation of the neutrophil lineage is warranted.Abbreviations G-CSF granulocyte colony-stimulating factor - GM-CSF granulocyte-macrophage colony-stimulating factor - HIV human immunodeficiency virus     

Analysis of the influence of therapy and viral suppression on high-risk sexual behaviour and sexually transmitted infections among patients infected with human immunodeficiency virus in Taiwan

This study examined the effects of certain characteristics of human immunodeficiency virus (HIV)-infected patients related to the risks of practising unprotected sex (UPS) among 919 HIV-infected patients who attended the sexually transmitted disease (STD) clinic of the Taipei City STD Control Center, Taiwan, during the period January–July 2004. After learning that they were HIV-positive, 517 (56%) subjects had practised UPS, 476 (52%) had a new STD diagnosis, and 106 (12%) had used some form of injected drug. UPS was reported by 76% of homosexual/bisexual males, 19% of heterosexual males and 5% of females, and was reported more often by those individuals with casual sexual partners (p < 0.001). According to multivariate logistic regression analyses, UPS was associated with male-tomale sexual intercourse (OR 2.46; 95% CI 1.26–4.86, p < 0.001), with casual sexual partners (OR 2.82; 95% CI 1.62–4.88, p < 0.001), and with an individual's knowledge of his/her HIV status for > 11 years (OR 2.06; 95% CI 1.02–4.18, p < 0.05). Although using anti-retroviral therapy to prevent sexual transmission of HIV is rational, the avoidance of at-risk sexual behaviour should also be a priority among HIV-seropositive individuals. Ongoing risk-reduction counselling related to HIV transmission is needed to reduce certain sexual behaviours associated with HIV transmission.     

Antibody-dependent cellular cytotoxicity and neutralizing activity in sera of HIV-1-infected mothers and their children.

The prognostic and protective role of antibodies mediating cellular cytotoxicity (ADCC) and neutralization was evaluated in sera of HIV-1-infected mothers and their consecutively followed children. The presence and titres of ADCC mediating and/or neutralizing antibodies in maternal sera did not predict HIV-1 infection in their respective children. No significant difference in the sera from the children was seen when comparing the presence of neutralizing antibodies between the uninfected and infected children. Stratification of the infected group according to clinical status revealed differences. Only one of 24 AIDS patients had a high neutralizing titre against IIIB. Four patients had a very low titre and the remaining had no detectable neutralizing antibodies at all. In contrast, 10/17 infected non-AIDS children had neutralizing antibodies. Similarly, no significant difference was seen when comparing the presence of ADCC-mediating antibodies between the uninfected and the infected group of children. However, a significantly higher frequency of ADCC was seen in the seropositive non-AIDS children compared with the AIDS children. This study clearly shows that the presence of antibodies mediating ADCC and neutralization in infected children, 0-2 years old, is associated with a better clinical status and delayed disease progression.     

Splenic smooth-muscle tumors in children with acquired immunodeficiency syndrome: report of two cases of this unusual location with evidence of an association with Epstein-Barr virus

Smooth-muscle neoplasms are rarely located in the spleen. They have been previously reported in five cases of children with human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS). Two cases of children with HIV infection/AIDS with autopsy and surgical pathology evidence of multiple smooth-muscle neoplasms with splenic involvement are presented. DNA was extracted from histology slides in both cases for analysis for Epstein Barr (EB) virus. In both cases, the presence of EB virus was confirmed. This paper documents two additional cases of the unusual phenomenon of splenic involvement by smooth-muscle neoplasms in the setting of AIDS in childhood and further supports the role of EB virus in the development of these neoplasms. Received: 27 January 1999 / Accepted: 23 August 1999     

Antibody- and complement-mediated lysis of HIV-infected cells and inhibition of viral replication

HIV-1-positive antisera were tested for their ability to lyse HIV-1-infected cells in the presence of active complement. Cytolytic effects caused by sera derived from infected humans were slower than those observed with sera from immunised chimpanzees. Lytic but also negative sera were found among HIV-1-infected asymptomatic men as well as among clinical AIDS cases. Human antisera that lysed infected cells reacted similarly irrespective of whether the complement was heterologous or autologous. Analysis of complement-mediated lysis using defined antisera against recombinant HIV-1 env or core antigens suggested that gp160/gp120 and p24 can act as target antigens for an antibody- and complement-mediated cytolysis of infected cells. Complement alone reduced the spread of HIV-1 infection in CD4+ cells and the ability of HIV-1 and HIV-2 to form plaques in CD4-transfected HeLa cells. Co-operative effects of specific antibodies and complement were the most effective in inhibiting HIV infections.     

Guidelines to avoid personnel contamination by infective agents in research laboratories that use human tissues

Summary The personnel in laboratories that utilize tissue and fluids from humans and other primates are at risk for infection with agents, including the viruses causing hepatitis, AIDS, and other infective agents such as mycobacteria tuberculosis. To minimize the chance of infection of laboratory personnel, carefully organized policies and procedures to minimize exposure to infective agents must be established in research laboratories. We outline some of the approaches of hospital clinical laboratories which have proved most effective in minimizing transmission of infections from samples to laboratory personnel. Also, we discuss simple considerations important in the use and in the selection of safety equipment. These guidelines and references to other safety information are provided to aid research laboratories in establishing safety procedures that will minimize chances of personnel contamination with infective agents from research samples.     

Altered IL-1 Expression and Compartmentalization in Monocytes from Patients with AIDS Stimulated with Mycobacterium avium Complex

The pathophysiologic basis for the exuberant intracellular growth of Mycobacterium avium complex (MAC) in AIDS patients is unclear but may relate to altered expression of modulatory cytokines. Interleukin (IL)-1, IL-6, and TNF- expression by monocytes from AIDS patients and healthy subjects (HS) stimulated with isogeneic MAC strains (SmT, smooth-transparent, virulent; SmD, smooth-domed, avirulent) was examined. Spontaneous cytokine production was not observed in patients with AIDS. MAC strains induced less IL-1 and IL-1 release in AIDS patients than HS (P < 0.05). The ratio of cell-associated to supernatant IL-1 also was increased in AIDS patients (P = 0.03). IL-1 mRNA expression paralleled protein release in either group of subjects. In both HS and AIDS patients, stimulation with SmD induced more IL-1 and TNF- release by monocytes compared to SmT. In AIDS patients, SmD also induced greater IL-6 release than SmT (P < 0.01). Alterations in monocyte expression and compartmentalization of the regulatory cytokines IL-1 and IL-6 may enhance bacterial replication and contribute to the patho-genesis of MAC infection in AIDS.     

Ultrastructural Changes Associated with Peripheral Neuropathy in HIV/AIDS

Light and electron microscopic studies were performed on neuromuscular biopsy specimens from 12 neurologically affected seropositive patients, 7 with the acquired immune deficiency syndrome (AIDS), 2 with AIDS-related complex, and 3 with no symptoms except for neuropathy. All patients had an axonal injury associated or unassociated with demyelination and peripheral neurogenic atrophy. Capillary lesions were consistently present, which seems to be a new finding. Moreover, tubuloreticular inclusions (TRIs) were found in endomysial (9 of 12 cases) and endoneurial (7 of 12 cases) vessels. Statistical analysis showed that TRIs in more than 20% of endomysial vessels correlated with a survival time shorter than 12 months (P = 0.028). Thus the quantification of TRIs seems to be one of the vital prognostic elements in this patient population.     

A mathematical simulation of the AIDS patient and extracorporeal detoxification

A simple numerical simulation of AIDS patient detoxification by a hypothetical extracorporeal device for the removal of viruses, infected white cells, and syncytia has been designed. The mathematical model accounts for healthy blood white cells attacking and destroying the viruses, while at the same time the viruses attack and infect certain white cells. The infected white cells serve as a site for viral growth; eventually the cells lyse, releasing a large number of viruses into the blood stream. The healthy white cells and infected white cells combine to form syncytia, where the virus multiplies, and finally the syncytium ruptures releasing all the virus. This model can be used to predict concentrations over a specified period for the patient. This is a mathematical model to be used as a research and design tool only.