Prophylaxis after occupational exposure to human immunodeficiency virus (HIV)

Reasons for seeking consultation among health care workers due to potential or supposed risk of HIV infection were analyzed. From August 1990 till July 1996 41 health care providers were consulted including: 22 nurses, 1 student of nursing college, 3 midwives, 4 laboratory workers and 7 physicians (surgeons and gynaecologist). Type of exposure to HIV and applying of safety precautions were evaluated in each case. In 10 cases the offer of postexposure prophylaxis with zidovudine was accepted (6 nurses, 1 student of nursing college, 3 surgeons). Exposure to HIV was described as: needlestick immediately after it was used in a HIV/AIDS patient, injury with a surgical needle while operating on an HIV infected blood. In the remaining cases the fear of HIV infection was due to work without protective gloves (nurses, laboratory workers), performing surgery on HIV (+) patient, (surgeons, nurses) or short-time contact of HIV infected blood with undamaged skin (nurses). Following conclusions can be drawn from our study: 1. Health care workers undertake safety precautions only when they are informed about HIV seropositivity of the patient. 2. Patients whose HIV serologic status is not known are considered not to create health risk for medical staff. 3. The level of knowledge of health care workers about risk of acquiring HIV infection, lack of risk and ways of diminishing the risk is poor. 4. None of followed health care workers was HIV-seropositive after occupational exposure to HIV.     

Accidental exposure to blood and the risk of transmission of virus infections for various occupational groups in Amsterdam, 1986-1996

Since 1986 the number of parenteral exposures to potentially infectious blood reported to the Amsterdam Public Health Service increases every year. The number of needlestick accidents increased significantly from 64 in 1986 to 166 in 1996 whereas the number of other exposures decreased from 59 to 44 in these years. The increase was mainly seen in nonhospital based (para)medics. A possible explanation of this increase is greater awareness of the potential infection risk with HIV, hepatitis B or C virus leading to a tendency to report more readily. This assumption is in contradiction with results of studies in hospital-based personnel where a decrease is observed as a result of educational programmes. Other explanations are a higher frequency of use of sharp instruments and (or) an increase in the workload. Out of a total of 1886 needlestick accidents in 1986-1996 one woman became HIV positive; she was deliberately infected by her ex-partner who injected her with blood of an AIDS patient, and one person contracted an hepatitis C virus infection: a policeman wounded by a needle used by a drug addict.     

The epidemiology of human immunodeficiency virus infection.

The epidemiology and natural history of infection with the human immunodeficiency virus (HIV) is reviewed. HIV is associated with a broad spectrum of disease, including AIDS. In presenting the natural history, early and late clinical manifestations, diagnosis of infection, incubation and latency periods, and survival time are discussed. Data from the published literature on the distribution of HIV infection in the adult U.S. population and factors that affect the acquisition and spread of the virus are also reviewed. Understanding of the epidemiology of this infection in certain high-risk groups is substantial and has provided a clear focus for preventive efforts and counseling. Many questions about spread in heterosexuals and about factors that may affect the natural history of the disease await completion of ongoing and planned studies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Accidental exposure of veterinary students to rabies

Accidental exposure to rabies occurred in more than 200 veterinary students at Texas A&M University from 1970 to 1977. Few of the animals to which the students were exposed had typical signs of rabies prior to the exposures. An accelerated preexposure rabies prophylaxis program coupled with retention of suspect tissues suitable for fluorescent antibody procedures has reduced the number of postexposure prophylaxis series.     

Accidental outcomes: Attitudinal consequences of workplace injuries.

A model of the attitudinal outcomes of the occurrence and severity of occupational injuries was developed and tested. The model postulates that workplace accidents result in a perceived lack of influence and a distrust of management, with the former also affecting the distrust of management. Both are hypothesized to predict job dissatisfaction. Exit (turnover intentions) and voice (perceptions of union instrumentality) are hypothesized as outcomes of job dissatisfaction. A sample of 9,908 employees was tested with the 1995 Australian Workplace Industrial Relations Survey database. Structural equation modeling provided strong support for the model with respect to accident occurrence, and the model was replicated across 8 different occupational groups. There was less support for the model with respect to accident severity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Virulence of human immunodeficiency virus

Virulence is relative capacity of a virus, compared to other closely related viruses, to produce disease in a host. Viral strains considered as virulent have been described in HIV-1 infected patients. They are characterized in vitro by enhanced cellular host range, rapid kinetic of replication and increased capacity of syncytium induction. Some genetic modification of the V3 loop in the envelope gene have been associated with the emergence of these strains. But at AIDS diagnosis, and even at the terminal stage of AIDS, only about half of the patients harbour syncytium inducing variants. There are much evidence for continuous viral replication throughout all stages of HIV-1 infection. There is no viral latency state in the natural HIV infection. This increasing viral burden might have a pivotal role in the pathogenesis of HIV disease. HIV-2 is less pathogenic than HIV-1. The nature of the viral determinants responsible for this reduced virulence remains unknown. In the simian immunodeficiency virus model, virulent and avirulent strains have been described and the nef gene seems to have a critical role in pathogenicity.     

Common themes of antibody maturation to simian immunodeficiency virus, simian-human immunodeficiency virus, and human immunodeficiency virus type 1 infections

Characterization of virus-specific immune responses to human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) is important to understanding the early virus-host interactions that may determine the course of virus infection and disease. Using a comprehensive panel of serological assays, we have previously demonstrated a complex and lengthy maturation of virus-specific antibody responses elicited by attenuated strains of SIV that was closely associated with the development of protective immunity. In the present study, we expand these analyses to address several questions regarding the nature of the virus-specific antibody responses to pathogenic SIV, SIV/HIV-1 (SHIV), and HIV-1 infections. The results demonstrate for the first time a common theme of antibody maturation to SIV, SHIV, and HIV-1 infections that is characterized by ongoing changes in antibody titer, conformational dependence, and antibody avidity during the first 6 to 10 months following virus infection. We demonstrate that this gradual evolution of virus-specific antibody responses is independent of the levels of virus replication and the pathogenicity of the infection viral strain. While the serological assays used in these studies were useful in discriminating between protective and nonprotective antibody responses during evaluation of vaccine efficacy with attenuated SIV, these same assays do not distinguish the clinical outcome of infection in pathogenic SIV, SHIV, or HIV-1 infections. These results likely reflect differences in the immune mechanisms involved in mediating protection from virus challenge compared to those that control an established viral infection, and they suggest that additional characteristics of both humoral and cellular responses evolve during this early immune maturation.     

Immunopathogenesis of human immunodeficiency virus

Human immunodeficiency virus (HIV) types 1 and 2 infect cells of the immune system and initiate a robust immune response which counteracts the viral spread but also accelerates the destruction of the immune system. Many pathogenic mechanisms have been proposed which include viral gene products, syncytium formation, direct virus killing of cells, apoptosis, autoimmunity, cytokine and chemokine expression, superantigens, virus directed cell-mediated cytolysis, and disruption of the lymphoid architecture. At present, there is no unifying theory or experimental proof of a single or a predominant mechanism for the pathogenesis of the HIV disease. This review is intended to highlight areas of HIV research relevant to the understanding of HIV immunopathogenesis.     

Behavioral determinants of occupational exposure to chemical agents.

Used the passive-active dimension of the job demand–control model (T. Theorell and R. A. Karasek, see record 83:28881) to examine the impact of behavioral factors on the exposure to and actual uptake of airborne lead in 2 lead exposed populations of male workers (18 from an electric accumulator factors and 18 from a lead smeltery) and to ascertain work-related determinants of hygienic behavior. Environmental exposure was assessed by measurement of the concentration of lead dust in ambient air at the workplace, and the intake of lead was assessed by measurement of the lead in blood level. In the work environment of Ss in active jobs, lower concentrations of lead in air were measures, but higher levels of lead in blood were observed in these workers. The opposite was true of workers in passive jobs. Differences in hygienic behavior (e.g., use of protective equipment) at work may explain these results. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inhibitors of human immunodeficiency virus integrase

In an effort to further extend the number of targets for development of antiretroviral agents, we have used an in vitro integrase assay to investigate a variety of chemicals, including topoisomerase inhibitors, antimalarial agents, DNA binders, naphthoquinones, the flavone quercetin, and caffeic acid phenethyl ester as potential human immunodeficiency virus type 1 integrase inhibitors. Our results show that although several topoisomerase inhibitors--including doxorubicin, mitoxantrone, ellipticines, and quercetin--are potent integrase inhibitors, other topoisomerase inhibitors--such as amsacrine, etoposide, teniposide, and camptothecin--are inactive. Other intercalators, such as chloroquine and the bifunctional intercalator ditercalinium, are also active. However, DNA binding does not correlate closely with integrase inhibition. The intercalator 9-aminoacridine and the polyamine DNA minor-groove binders spermine, spermidine, and distamycin have no effect, whereas the non-DNA binders primaquine, 5,8-dihydroxy-1,4-naphthoquinone, and caffeic acid phenethyl ester inhibit the integrase. Caffeic acid phenethyl ester was the only compound that inhibited the integration step to a substantially greater degree than the initial cleavage step of the enzyme. A model of 5,8-dihydroxy-1,4-naphthoquinone interaction with the zinc finger region of the retroviral integrase protein is proposed.     

CD4-Induced conformational changes in the human immunodeficiency virus type 1 gp120 glycoprotein: consequences for virus entry and neutralization

Human immunodeficiency virus type 1 (HIV-1) entry into target cells involves sequential binding of the gp120 exterior envelope glycoprotein to CD4 and to specific chemokine receptors. Soluble CD4 (sCD4) is thought to mimic membrane-anchored CD4, and its binding alters the conformation of the HIV-1 envelope glycoproteins. Two cross-competing monoclonal antibodies, 17b and CG10, that recognize CD4-inducible gp120 epitopes and that block gp120-chemokine receptor binding were used to investigate the nature and functional significance of gp120 conformational changes initiated by CD4 binding. Envelope glycoproteins derived from both T-cell line-adapted and primary HIV-1 isolates exhibited increased binding of the 17b antibody in the presence of sCD4. CD4-induced exposure of the 17b epitope on the oligomeric envelope glycoprotein complex occurred over a wide range of temperatures and involved movement of the gp120 V1/V2 variable loops. Amino acid changes that reduced the efficiency of 17b epitope exposure following CD4 binding invariably compromised the ability of the HIV-1 envelope glycoproteins to form syncytia or to support virus entry. Comparison of the CD4 dependence and neutralization efficiencies of the 17b and CG10 antibodies suggested that the epitopes for these antibodies are minimally accessible following attachment of gp120 to cell surface CD4. These results underscore the functional importance of these CD4-induced changes in gp120 conformation and illustrate viral strategies for sequestering chemokine receptor-binding regions from the humoral immune response.     

Interactions between the human immunodeficiency virus and hepatitis C virus

INTRODUCTION: Prevalence of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected subjects is around 9%, varying according to the mode of contamination. Reciprocal interactions between the two viruses have to be evaluated. CURRENT KNOWLEDGE AND KEY POINTS: HCV infection is usually associated with chronic hepatitis and detectable viremia in HIV-infected patients. HIV infection enhances HCV replication, leading to more severe liver lesions and to a more rapid occurrence of cirrhosis. This underlines the need for both early diagnosis and therapy in order to avoid severe evolution of the liver disease. FUTURE PROSPECTS AND PROJECTS: Even though the rate of long-term responses to interferon alpha is low, improvement may be expected from combined therapies, especially with combination including ribavirin. The impact of both antiretroviral triple therapy and accompanying immune restoration on natural history and treatment of HCV infection has to be assessed, as the above mentioned consensual conclusions may be modified in a near future.     

Dicaffeoylquinic acid inhibitors of human immunodeficiency virus integrase: inhibition of the core catalytic domain of human immunodeficiency virus integrase

Integration of a cDNA copy of the human immunodeficiency virus (HIV) genome is mediated by an HIV-1-encoded enzyme, integrase (IN), and is required for productive infection of CD4+ lymphocytes. It had been shown that 3,5-dicaffeoylquinic acid and two analogues were potent and selective inhibitors of HIV-1 IN in vitro. To determine whether the inhibition of IN by dicaffeoylquinic acids was limited to the 3,5 substitution, 3,4-, 4,5-, and 1,5-dicaffeoylquinic acids were tested for inhibition of HIV-1 replication in tissue culture and inhibition of HIV-1 IN in vitro. All of the dicaffeoylquinic acids were found to inhibit HIV-1 replication at concentrations ranging from 1 to 6 microM in T cell lines, whereas their toxic concentrations in the same cell lines were > 120 microM. In addition, the compounds inhibited HIV-1 IN in vitro at submicromolar concentrations. Molecular modeling of these ligands with the core catalytic domain of IN indicated an energetically favorable reaction, with the most potent inhibitors filling a groove within the predicted catalytic site of IN. The calculated change in internal free energy of the ligand/IN complex correlated with the ability of the compounds to inhibit HIV-1 IN in vitro. These results indicate that the dicaffeoylquinic acids as a class are potent and selective inhibitors of HIV-1 IN and form important lead compounds for HIV drug discovery.     

Zidovudine pharmacokinetics in premature infants exposed to human immunodeficiency virus

We used population analysis techniques to determine zidovudine (ZDV) pharmacokinetic parameters in 15 preterm neonates (mean gestational age, 29.4 weeks; mean birth weight, 1,230 g) at a mean age of 5.5 days. The values of the pharmacokinetic parameters were as follows: clearance, 2.53 +/- 0.44 ml/min/kg; volume of distribution, 1.59 +/- 0.51 liters/kg; and half-life, 7.2 +/- 1.5 h. For seven infants studied a second time, at a mean age of 17.7 days, an increase in the mean clearance (2.33 versus 4.35 ml/min/kg; P = 0.024) and a decrease in the half-life (7.3 versus 4.4 h; P = 0.003) were found. The ZDV clearance is low and the half-life is prolonged in premature neonates, but the clearance increases and the half-life decreases with postnatal age. Potentially toxic concentrations may accumulate in serum if the standard dosage for full-term infants is used. We suggest that initial ZDV dosing should be reduced to 1.5 mg every 12 h for preterm neonates.