In vitro characterization of various heat-treated prothrombin complex concentrates (PCC)

All of 6 heat-treated prothrombin complex concentrates (PCC) tested contained adequate levels of factor IX but factor VII content was low. Levels of factors II, X, protein C and protein S were variable and antigen levels were always greater than those of functional activities. On crossed-immunoelectrophoresis factor IX showed variable anodal shift in all concentrates tested and in some activated factor IX was demonstrated by immunoblotting technique. These findings suggested some activation and/or denaturation during production and/or heating. Modest amount of factor VIII clotting activity by solid-phase amidolytic method and of factor VIII antigen was demonstrated in some concentrates but none contained more than a trace factor VIII inhibitor bypassing activity. The results suggested that heat-treated PCC should provide safe therapeutic products for hemophilia B.     

High risk of acquired immune deficiency syndrome (AIDS) and of AIDS related complex (ARC) in hemophiliacs seropositive for more than 5 years

A group of 90 hemophiliacs who had been regularly treated with non virus-inactivated factor VIII or IX concentrates were studied in 1983. At that time 50 patients were HIV-1-antibody positive, 6 additional seroconversions occurred until 1985. 26 of the 50 patients seropositive in 1983 are currently asymptomatic. 4 patients have developed the lymphadenopathy syndrome, 9 patients AIDS and 11 patients ARC (CDC IV C 2). 6/9 cases of AIDS and 10/11 cases of ARC have occurred only after 1985. Patients, who subsequently became symptomatic, had significantly higher IgG levels in 1983, otherwise no predictive laboratory tests were identified. Patients with T4 counts above 500/microliters became symptomatic later, but after 5 years the incidence of AIDS was comparable in patients with original T4 counts of more than or below 500/microliters.     

Does HHV-8 have a protective role on the development of HIV encephalopathy? Italian HIV-Seroconversion Study

OBJECTIVE: To evaluate risk factors for HIV encephalopathy and whether Kaposi's sarcoma (KS) and coinfection with human herpesvirus 8 (HHV-8) protect against this disease in a cohort of HIV seroconverters. METHODS: Individuals with known dates of HIV seroconversion belonging to different HIV exposure categories (intravenous drug users, homosexual men, heterosexual contacts) were recruited by 17 clinical centers throughout Italy. Antibodies to HHV-8 lytic antigens were detected in a subgroup of participants using an immunofluorescence assay. Risk factors for HIV encephalopathy were evaluated using Cox proportional models. The association between KS or HHV-8 infection and HIV encephalopathy was evaluated using standard statistical techniques. RESULTS: During the study period, 485 of the 1,520 participants developed acquired immunodeficiency syndrome, 38 of whom developed HIV encephalopathy. HHV-8 serologic status was determined for 390 participants. Male gender, injecting drug use, and low CD4 T-cell count were associated with HIV encephalopathy; none of the 63 participants with KS developed this disease. The risk of HIV encephalopathy did not differ significantly by HHV-8 serologic status. CONCLUSIONS: HIV encephalopathy was found to be associated with male gender and intravenous drug use. The risk increased at lower CD4 T-cell counts. Although HIV encephalopathy occurred less frequently in patients with KS, no association with HHV-8 infection was found.     

A prospective study of HIV-infected haemophilic boys and the prognostic significance of immune and haematological abnormalities

Fifty-seven haemophilic boys have been studied prospectively determining T lymphocyte subsets and haematological parameters over a period of 26 months. Clinical follow up of these patients has continued for a further 41 months. At the beginning of the study 21 boys were HIV antibody seropositive and seroconversion was documented in a further 9 during the study period, giving a 52.6% incidence of HIV seropositivity. It has been possible to define a group of patients with persistently falling T4 values and these have shown clinical evidence of HIV infection. Although persistent generalized lymphadenopathy has been observed in 30% of HIV antibody positive boys and some boys have had unexplained fevers, only one boy has progressed to have the acquired immune deficiency syndrome (AIDS) some 5 years and 3 months from HIV seroconversion. This boy had a persistently falling T4 value. The importance of these findings is discussed. To date the abnormalities found in these haemophilic boys irrespective of their age are similar to those already reported in adult haemophiliacs.     

Surveillance for bloodborne infections

At the close of the 20th century, the blood supply in the U.S. is among the safest in the world. Multifaceted and overlapping strategies that include comprehensive donor history-taking and screening (soon to include nucleic acid testing for HCV and HIV), and viral inactivation of plasma derivatives have resulted in significant declines in transfusion-transmitted infections. Nonetheless, we and our blood supply remain vulnerable to new or re-emerging infections as a consequence of changes in human behavior and demographics, improvements in technology and industry, economic development and land use, and microbial change. The second phase of CDC's strategic plan to improve our national capacity against emerging infectious diseases targets diseases transmitted through blood and blood products as one of its nine special focus areas. One of our mainstays against emerging threats must include surveillance, integrated with a multi-disciplinary approach that includes epidemiology and laboratory sciences. Enhanced surveillance can play an important role in helping to ensure the continued safety of blood and plasma products.     

CD4 cells in HIV-1 infected hemophiliacs: effect of factor VIII concentrates.

The goal of this study was to determine the long-term clinical outcome of Human Immunodeficiency Virus (HIV) infection in a group of HIV-seropositive hemophiliacs for whom the dates of seroconversion were known and to investigate whether the use of monoclonal antibody purified factor (high purity) concentrate and treatment with zidovudine may alter the effect of HIV infection in seropositive hemophiliacs. Twenty-eight hemophiliacs were followed for up to 9 years after seroconversion. In addition, 13 seropositive patients who elected to receive (high purity) factor VIII concentrate for up to 1.5 years were compared to a contemporaneous concurrent control group of 8 seropositive patients treated with intermediate purity factor VIII concentrate, and then both groups were followed for an additional 1.5 years while receiving zidovudine. The acquired immunodeficiency syndrome (AIDS) developed in 9 of 28 patients (33%) from 1 to 9 years following seroconversion. CD4 cell count declined at a rate of 13.5% per year for the cohort but for persons 25 years and above the rate was significantly higher (17.5 +/- 9.2% per year vs. 9.5 +/- 4.7%, mean +/- SD, p less than 0.05) than in those under 25. All three patients who had undergone splenectomy developed AIDS. Subjects treated with high purity concentrates, with the exception of one patient who developed the nephrotic syndrome secondary to amyloidosis, had stable CD4 cell counts. On the other hand, all patients receiving intermediate purity concentrates had a decline in CD4 cells, and the difference from initial levels was highly significant (p = 0.01). The CD4 cell concentrations in these patients were stable after treatment with zidovudine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Assessment for evidence of non a-non b hepatitis in patients given n-heptane-suspended heat-treated clotting factor concentrates

Nineteen patients, (2 adults, 17 children) with inherited bleeding disorders were infused with n-heptane-suspended-heated clotting factor concentrates. Twelve of the nineteen were previously untreated. Six patients were infused with Profilnine Heat-Treated® and 13 with Profilate Heat-Treated. Five separate centers participated and were given various lots of concentrates for use. Blood from the seventeen children was sampled prior to entry, at infusion, 2 weeks, 6 weeks, 12 weeks and 6 months after the first infusion. The two adults were sampled every 2 weeks. Twelve of the 19 patients were followed beyond six months. Three patients demonstrated a rise in ALT during the first six months of observation with levels above 2.5 times the upper limit of normal. One of these patients showed a parallel increment in a-CMV IgM titer and a second patient, an adult, had previously received many units of single donor blood components. During the second 6 month observation interval, two patients showed a rise in ALT. One of these patients had been exposed to only one lot of concentrate with no other viral cause being determined. Two additional patients had a moderate increase in ALT up to 98 U/L (normal <50). No patients were clinically ill or showed jaundice during these episodes. The hepatitis episode at 11 months in the patient using one lot of concentrate, might suggest a non-viral mechanism in this instance. This study indicates that these concentrates may be associated with episodes of ALT above 2.5 times the upper limit of normal in approximately 20% of the patients treated, but the etiology of the raised ALT may not always be Non A-Non B hepatitis.     

Bilateral amyotrophic neuralgia (Parsonage Turner syndrome) with HIV seroconversion

We report a unusual case of neuralgic amyotrophy (NA) occurring during the seroconversion stage of an HIV infection. Combined with previously published cases, our observation suggests that NA associated with HIV could belong to the group of early multiplex mononeuritis. Neurologists should be aware of HIV infection when managing a patient with NA.     

Survey on Drug Use Among People Living with HIV in Hong Kong

This study investigated the prevalence of drug use and the drug use behavior among people living with HIV in Hong Kong. In this cross-sectional survey, subjects were recruited by convenience sampling from the out-patient clinic of a HIV treatment center. A total of 500 subjects completed the questionnaire between January and May 2017. About one third (31.4%, n?=?157) participants reported drug use behavior. Common substances used included methamphetamine (65%), rush poppers (59.2%), gamma-hydroxybutyrate (56.7%), ketamine (49%), ecstasy (45.9%), cannabis (34.4%), cocaine (18.5%), cough medicine (15.3%), and heroin (7%). Polydrug use was common (51%). Younger age, men who have sex with men, history of sexually transmitted infections, and smoking were independently associated with drug use. About 34.4% drug users had co-existing mental illnesses. Most drug users (91.1%) had never received any form of drug treatment services. Linking HIV-infected drug users to drug addiction treatment services is needed.     

Development of a heat-treated factor VIII/von Willebrand factor concentrate prepared from heparinized plasma

A high yield, intermediate purity factor VIII concentrate derived from heparinized plasma has been developed which can be heat-treated at 60 degrees C, 68 degrees C or 80 degrees C/72 h to permit inactivation of viral contaminants which may be present. After cold reprecipitation of the heparinized cryoprecipitate (CRC), the resolubilized CRC precipitate was adjusted to 25-30 mg/ml protein and pH 6.35 +/- 0.1 and incubated for 1 h at 8 degrees C. After centrifugation to remove the precipitated fibrinogen and fibronectin, a factor VIII-rich supernatant can be recovered which contains greater than 500 units of VIII:C per liter of starting plasma (Method I product) at a purity of 1.5 U/mg protein. Adjusted to 50 mM glycine and pH 6.8, the product can be lyophilized and heat-treated at 60 degrees C/72 h without a significant loss of VIII:C activity. However, at 68 degrees C or 80 degrees C/72 h, temperatures now reported to be more effective in viral inactivation, the recoveries were reduced to 68 and 33% respectively. Significantly improved recoveries after heat-treatment (HT) at 68 degrees C or 80 degrees C/72 h were achieved if the 8 degrees C supernatant product was prepared by a modified procedure (Method II). This further reduces the fibrinogen content of the product while maintaining VIII:C yields greater than 500 U/l at a purity of 1.9 U/mg. When adjusted to 50 mM glycine and 1-2% (w/v) sucrose (pH 6.8), lyophilized and heat treated at 60 degrees C, 68 degrees C or 80 degrees C/72 h, the VIII:C recoveries of Method II product were 88-100%, 79-84% and 80-83% of pre-HT levels respectively. The yield of VIII:C was greater than 400 U/l at a purity of 1.6-1.4 U/mg at 1-2% (w/v) sucrose even after the severe heat-treatment at 80 degrees C. In addition, the von Willebrand factor multimers are similar in size and triplet pattern to those observed in routine cryoprecipitate preparations.     

Substance Use and Other Psychiatric Disorders in Impaired Practitioners

This paper describes the nature and comorbidity of substance use and other psychiatric disorders in 157 impaired practitioners notified to the Medical Practitioners Board of Victoria from 1983 to 1997. Diagnoses were reduced to three diagnostic categories, viz, substance use disorder (n = 62), other psychiatric disorder (n = 62), and combined substance use and other psychiatric disorder (n = 33). Sixty nine percent of those with other psychiatric disorders suffered either bipolar disorder (n = 27), schizophrenia (n = 22), or depression (n = 17). Psychiatric comorbidity in drug-related diagnoses was 26% and in alcohol-related diagnoses 64%. Sixty five percent of substance use disorders were notified more than 12 months after onset of impairment, and 49% of all practitioners (71% with substance use disorder) did not receive treatment prior to notification. This combined with a high relapse rate (41%) makes some impaired practitioners a risk to their patients.     

Intrathecal synthesis of anti-HIV antibodies in AIDS patients

We studied the production within the CNS of anti-HIV antibodies, of non-specific IgG, and the presence of HIV antigens in the serum and CSF of 28 HIV infected patients belonging to group IV in the Center for Disease Control classification. CSF and serum were diluted under optimal conditions to equalize their IgG content, to enable us to better interpret serum and CSF reactivity by means of Western blot and ELISA. Under these conditions, no patient displayed a limited immunological response profile in CSF as compared to serum. On the contrary, there was intrathecal synthesis (ITS) of anti HIV-antibodies in Western blot test in 21 patients for gp160 and ITS was demonstrable for env, gag, and pol products. ITS of anti-HIV antibodies occurred in 17 patients when measured by ELISA. ITS of non specific IgG and HIV-antigens in CSF were less frequent. A marked anti-HIV response is evident in the CSF-CNS compartment in the later phases of the HIV infection.     

HIV-related opsoclonus–myoclonus–ataxia syndrome: Report on two cases

Opsoclonus–myoclonus–ataxia (OMA) syndrome is a rare neurological disorder, characterized by a rapid onset of generalized myoclonus in association with chaotic multi-directional eye movements and, less frequently, cerebellar ataxia. OMA is commonly related to a paraneoplastic process, specifically neuroblastoma in children and lung or breast cancer in adults. Nevertheless, OMA may occur in association with various infectious agents, such as Coxsackie virus B3, Epstein-Barr virus, mumps, enterovirus, and streptococcus. We recently encountered two cases of HIV-related OMA syndrome. The first patient developed a sudden onset of OMA at the time of HIV seroconversion. The second patient experienced severe ataxia with a mild degree of myoclonus and opsoclonus, associated with an elevated CD4 count following the initiation of highly active antiretroviral therapy (HAART). We suggest that OMA syndrome may be another rare manifestation of HIV infection at the time of seroconversion or during an immune restoration period.     

Predicting substance use in late adolescence: results from the Ontario Child Health Study follow-up.

OBJECTIVE: The purpose of this study was to evaluate the relationship between use of tobacco, alcohol, marijuana, and hard drugs (substance use) and psychiatric disorder in early adolescence and substance use in late adolescence. METHOD: Adolescents included in the study were identified by means of a household sampling frame and participated in the Ontario Child Health Study in 1983 and the follow-up in 1987. There were 726 12-16-year-olds (369 boys and 357 girls) in 1983 who had complete information in 1987. Data on substance use were collected from adolescents by using a structured, self-administered questionnaire. Data on psychiatric disorder were collected in 1983 from both adolescents and their parents by using problem checklists to assess conduct disorder, attention deficit disorder, and emotional disorder. RESULTS: Prior substance use in 1983 was associated strongly with subsequent use in 1987. Among the psychiatric disorders assessed in 1983, only conduct disorder made an independent contribution to predicting use of marijuana (relative odds = 3.46) and other hard drugs (relative odds = 6.82) in 1987, after prior use of these substances and coexisting attention deficit and emotional disorders were controlled. Corresponding estimates of attributable risk (the expected contribution of exposure to conduct disorder to the development of substance use) were 5.7% and 11.1%, respectively. CONCLUSIONS: Although a statistically significant relationship existed between conduct disorder in early adolescence and use of marijuana and hard drugs in late adolescence, the potential is limited for preventing substance use in the general population by treating conduct disorder early on.     

Characteristics of HIV-positive chronically mentally ill inpatients

The growing population of chronically mentally ill persons who are HIV-positive or who have AIDS has not yet been adequately studied. We describe the entire population of known HIV-positive inpatients in a state psychiatric center in New York City. In this sample, the typical patients with known HIV infection is as likely to be a man as a woman and is a member of an ethnic minority group. HIV-positive patients had multiple risks for HIV infection including injecting drug use (IDU), sex with IDU partners, prostitution and male homosexual activity. Most patients were at a late stage of HIV-infection, typically with CD4+ cell counts of 400. Discharge plans were complicated by HIV illness and most HIV-positive patients had a longer length of hospital stay than non HIV-positive patients. We discuss the need to plan for the management of increasing numbers of HIV-positive patients in inpatient, outpatient, and residential facilities.At the time of this study Dr. Meyer was research coordinator; Dr. Empfield was clinical director; and Ms. Engel was research assistant at Creedmoor Psychiatric Center; Dr. Cournos is director, Washington Heights Community Service at New York State Psychiatric Institute.     

Upregulation of microglia in drug users with and without pre-symptomatic HIV infection

It is generally thought that infection of the central nervous system (CNS) by HIV-1 can occur early, even around the time of seroconversion, and evidence from animal studies supports this. However, the mode and timing of viral entry remain poorly understood since there have been comparatively few studies of the early neuropathology of HIV infection. In this study, samples of frontal and temporal lobes, and basal ganglia, were selected from 12 HIV-positive drug users who had been infected for 4-130 months before death, 10 HIV-negative drug users and 10 non-drug using controls, all age and sex matched. Routine and immunocytochemical staining showed that leptomeningeal and perivascular lymphocytic infiltrate was upregulated in HIV-infected cases compared with the two control groups, and choroid plexitis was confined to the HIV-positive subjects, suggesting an association with viral infection. In contrast, CD68-positive microglia were enhanced in both HIV- positive and HIV-negative drug users, considerably above the baseline seen in normal controls. However, there was no statistical difference between the three groups in relation to astrocytes. Screening and competitive polymerase chain reaction (PCR) undertaken on multiple samples including brain tissue, choroid plexus and leptomeninges from four of the HIV-positive subjects and one control case showed that the pro-viral burden was never more than 13 copies/microg DNA and was negative in multiple samples from one HIV-positive case and one control case. All the basal ganglia samples were PCR-negative. This study has not revealed any t spots' of viral load in brain tissue, choroid plexus or meninges, either early or late in the course of pre-symptomatic HIV infection. Drug use alone is associated with significant upregulation of microglia and this may predispose to HIV infection of the nervous system in drug users.     

Transmission of HIV and AIDS by plasmapheresis for Guillain-Barré syndrome

A 58-year-old patient suffering from Guillain-Barré syndrome was successfully treated with plasma exchange therapy. Two- and half year later she developed AIDS. The only risk factor of this patient was plasmapheresis and it appeared, retrospectively, that one of the plasma donor samples contained antibodies to HIV. Knowing the exact moment of infection of our patient we documented the transfer of HIV antibodies from donor to patient, a HIV antigen peak two weeks after transmission (reflecting the initial virus replication in the patient) and subsequently the occurrence of patients' HIV antibodies and the reoccurrence of HIV antigen at the moment AIDS was diagnosed.     

Relationship between alcohol use/abuse, HIV infection and neuropsychological performance in African American men

This study examines the impact of alcohol use and HIV infection on neuropsychological performance in a sample of 497 community-resident African American men. HIV serostatus and alcohol use (during the past 12 months) exerted an interactive effect on psychomotor speed, reaction time, and motor speed, and in general, HIV infected heavy drinkers evidenced significantly poorer performance than other HIV positive subjects. Main effects for HIV serostatus were noted for reaction time, with seronegative men performing better than seropositives. This study examines a sample of men who continue to show increases in HIV infection, however, sample specific issues such as comorbid substance use, past histories of head injury, and lack of data on alcohol abuse and dependence require caution in definitively attributing the findings solely to alcohol and HIV. However, these findings suggest that relatively recent heavy alcohol use may represent a potential risk factor for more rapid or pronounced cognitive decline in HIV positive individuals, and that these patterns may be even more pronounced in persons with comorbid substance use.     

Understanding associations between serious mental illness and HIV among patients in the VA Health System

OBJECTIVE: This study compared the recorded prevalence of HIV among veterans with and without serious mental illness. METHODS: This cross-sectional study examined data from a national sample of veterans who received a diagnosis of serious mental illness (schizophrenia, bipolar disorder, and other, nonorganic psychoses) in fiscal year 2002 (FY2002) (N=191,625) and from a national random sample of veterans in FY2002 who did not receive serious mental illness diagnoses (N=67,965). Logistic regression was used to evaluate the recorded prevalence and predictors of HIV. RESULTS: HIV diagnoses were recorded for 1.0% of patients with serious mental illness and .5% of patients without serious mental illness. Multivariate analyses indicated that individuals with bipolar disorder were no more likely than those without serious mental illness to have a recorded HIV diagnosis (OR=1.08, CI=.93-1.24), whereas those with other psychoses were more likely to have one (OR=1.18, CI=1.01-1.38). An interaction was observed between schizophrenia and substance use disorder. Compared with patients who had neither schizophrenia nor a substance use disorder, those with schizophrenia without a substance use disorder were less likely to have a recorded HIV diagnosis (OR=.49, CI=.42-.58), whereas those with a substance use disorder were more likely to have a recorded HIV diagnosis (OR=1.22, CI=1.04-1.43). CONCLUSIONS: Despite the elevated crude recorded prevalence of HIV, multivariate analyses suggested that HIV-related risk factors underlie the associations between HIV and the serious mental illness diagnoses. For patients with schizophrenia, this study is the first to demonstrate reduced HIV risk in the absence of a substance use disorder.