Transmission of human immunodeficiency virus (HIV) by blood transfusions screened as negative for HIV antibody

Since early 1985, blood donations in the United States have been screened for antibody to human immunodeficiency virus (HIV). To identify instances of HIV transmission by antibody-negative donations, we investigated 13 persons seropositive for HIV who had received blood from 7 donors who were screened as negative for HIV antibody at the time of donation. Twelve of the 13 recipients had no identifiable risk factors for HIV infection other than the transfusions they had received. On evaluation 8 to 20 months after transfusion, HIV-related illnesses had developed in three recipients, and the acquired immunodeficiency syndrome had developed in one. All seven donors were found to be infected with HIV. On interview, six reported a risk factor for HIV infection, and five had engaged in high-risk activities or had had an illness suggestive of acute retroviral syndrome within the four months preceding their HIV-seronegative donation. Thus, these donors had apparently been infected only recently, and so were negative at the time of blood donation according to available antibody tests. We conclude that there is a small but identifiable risk of HIV infection for recipients of screened blood. To minimize this risk, the reasons for deferral of donation need to be communicated more effectively to blood donors who are at high risk of HIV infection, and new assays that detect HIV infection earlier should be evaluated for their effectiveness in screening donated blood.     

Endocrine consequences of infection by human immunodeficiency virus (HIV)

The acquired immunodeficiency syndrome (SIDA) is a severe multivisceral affection that is sometimes composed of a clinical expression compatible with an endocrine insufficiency. The post-mortem verifications confirmed the high frequency of the suprarenal, pituitary and testicular lesions. The hormonal functional exploration confirmed the possibility of a decrease in the cortical suprarenal function that contrasts with a moderate hypercortisolemia and an hypogonadism without elevation of the gonadotrophins. The clinical expression of the deficits is unusual. Nevertheless a few cases of obvious suprarenal or antepituitary insufficiency bond to a secondary inflammatory necrosis, an infection by CMV, or a toxoplasmosis have been reported. More often, these hormonal alterations are moderate. There mechanisms are still imprecise. The non-specific response to the stress led by the disease doesn't give an explanation to the observed abnormalities. The described existence of antihormone antibodies in AIDS or the secretory potentialities of the activated lymphocytes might contribute to the physiopathology of the endocrine modifications outside of any infections or endocrine metastatical localisation.     

Allergic manifestations of human immunodeficiency virus (HIV) infection

Drug allergy is the most common and significant allergic manifestation of HIV³ infection. Initially described in patients treated with SMX-TMP for PCP, allergy is now known to involve a multitude of drugs. The pathogenesis of, and risk factors for, allergy in HIV infection are poorly understood, although there is evidence suggesting that allergy is more common with advancing immunodeficiency. HIV-negative subjects with sulfonamide allergy may have drug-specific antibodies and drug metabolite-induced lymphocyte cytotoxicity, abnormalities that could partly explain the allergic mechanisms and which may have future diagnostic potential; these abnormalities have not been described in HIV-infected subjects. Therapy includes avoidance, suppressive agents such as corticosteroids, and desensitization, although the appropriate role for each is not entirely clear. Serum IgE levels have been shown to rise with progressive disease; those patients with higher levels may have a worse prognosis. The mechanisms of this rise are multifactorial, probably a combination of altered T-lymphocyte regulation of IgE synthesis and of production of specific IgE directed against microbial antigens.     

Cytokine regulation of the human immunodeficiency virus (HIV)

The remarkable ability of HIV to insinuate itself into the working of the immune system is the key of its success as an infectious agent. Given that the cytokine network regulates the immune responses, it is not surprising that cytokines can modulate HIV infection. GM-CSF, IL6 and TNF-α enhance HIV, but TGF-β and HIF inhibits the virus. However, the anti-HIV activity of TGF-β is restricted to myeloid cells, while HIF inhibits HIV in myeloid cells and in T-lymphocytes. HIF is produced by CEM cells after induction by an extract from pine cones. It is not an interferon and is likely a novel cytokine. It is pepsin-sensitive but trypsin-resistant and has an apparent molecular weight of 7–12 KDa. Apart from having anti-HIV activity, crude preparations of HIF also inhibit HTLV-1 virus but not HSV virus replication.     

Electron microscopy of human hepatitis B virus cores by negative staining-carbon film technique

The ultrastructure of the nucleocapsid component of human hepatitis B virus (core particle) was studied by negative staining-carbon film technique. Using this method an improved image of core particles was obtained in respect of resolution and contrast. Two-dimensional crystalline arrays of core particles were formed in vitro. Under these arrays the distance between the particle centers was 28.3 nm, corresponding to the capsid diameter, when analyzed through optical diffraction patterns. Positively stained images of these arrays revealed that core particles contain an electron-dense center of nucleoid-like area about 21 nm in diameter. The capsid surface rarely exhibited small capsomeres, ie, small spheres or ring-like structures measuring 4.0–4.2 nm. From the dimension of these structures and the analysis by Markham's rotational technique, it was suggested that each of these capsomeres is an individual subunit (monomer) and 180 of these subunits build up the core particle capsid according to the icosahedral symmetry (T = 3), but not clustering into distinct morphological features.     

Serum IgE and human immunodeficiency virus (HIV) infection

Human immunodeficiency virus infection is characterized by a progressive depletion of helper T-lymphocytes and, like allergic diseases, is associated with altered T cell regulation. Total serum IgE was measured in 67 infected male subjects, 27 uninfected heterosexual male subjects, and 18 uninfected homosexual male subjects. The mean IgE level (132 IU/ml) of infected subjects with a helper T-lymphocyte number less than or equal to 200/mm3 was significantly greater than mean IgE levels of the uninfected heterosexual (38 IU/ml) and homosexual (35 IU/ml) groups. IgE levels were inversely related to both helper T cell and suppressor/cytotoxic T cell numbers but not to IgG or IgA levels. The increase in IgE was not a reflection of an increased prevalence of atopic disease (allergic asthma, allergic rhinitis, or atopic dermatitis) in the infected subjects. The elevation of IgE may be related to a difference among the groups in T cell production of IgE regulatory lymphokines.     

Serological survey of human immunodeficiency virus (HIV) in Ethiopia

The presence of anti-human immunodeficiency virus 1 antibodies was tested in 5,565 serum samples from Ethiopia of which 5,265 were collected from military recruits in the framework of a hepatitis B (HBV) seroepidemiological study performed on a national scale in 1985-1986; the remaining were 300 sera from a population of outpatients belonging to the Arsi region. Of the 5,565 sera, 121 (2.1%) were found to be repeatedly reactive by enzyme-linked immunosorbent assay (ELISA) test for HIV-1 antibodies, but these reactivities were confirmed by Western Blot (WB) assay in only four cases (0.07%) and by ENVACOR (confirmatory competitive ELISA) in three samples. Twenty-three sera were positive by WB to one or two bands related to core proteins but were all negative by ENVACOR. However, according to accepted criteria for positivity, these sera must be regarded as indeterminant reactors. A sample of 409 sera, both reactive and nonreactive by HIV-1 ELISA, were further tested for antibodies to HIV-2 by ELISA. Reactive sera were analysed by WB and by radioimmunoprecipitation assay (RIPA) using 35S-cysteine metabolically labelled SIVmac (HTLV-IV) infected cell lysates. Only 11 sera were found to be slightly reactive in ELISA, but this was not confirmed by WB or RIPA. Data indicate that HIV infection was not widespread in the general population of Ethiopia up to 1986.     

Serotyping of human astrovirus strains by immunogold staining electron microscopy

Human astrovirus strains were propagated in CaCo-2 cell cultures, and virus multiplication was demonstrated by immunosorbent electron microscopy (ISEM). Serotyping of the virus strains was carried out in cell culture fluids or directly in faecal extracts by an indirect immunogold staining (IGS) electron microscopy technique, using specific rabbit antisera against astrovirus types 1–6 as primary antibodies and goat anti-rabbit IgG gold conjugate as secondary antibody. Thirty-seven astrovirus strains were examined, of which 26 grew in the cell cultures in several passages. IGS of the cell-derived viruses showed that 16, 3, 3, and 4 of the strains were types 1, 2, 3, and 4 respectively. Types 5 and 6 were not demonstrated. Eleven strains did not grow in cell cultures, and attempts to serotype these strains by IGS directly in the faecal extracts were unsuccessful, except for one strain which was found to be type 1. The results indicate that IGS may be a specific and suitable method for serotyping astroviruses grown in cell cultures.     

T-cell lymphoma associated with human immunodeficiency virus (HIV) infection

A patient with pneumococcal septicaemia and serological evidence of infection with human immunodeficiency virus (HIV) presented with a peripheral T-cell lymphoma. As far as we are aware this association has not been reported previously.     

Haematological abnormalities in human immunodeficiency virus (HIV) disease.

Peripheral blood and bone marrow changes are commonly seen in disease associated with human immunodeficiency virus (HIV). This annotation aims to summarise these changes and to suggest possible factors entailed in their occurrence.     

Isolation of human immunodeficiency virus (HIV) from plasma during primary HIV infection

Human immunodeficiency virus (HIV) has been isolated from plasma in 6 of 7 patients showing clinical symptoms of a primary HIV infection. Parallel cultures from peripheral blood mononuclear cells (PBMC) yielded virus in 5 patients. In one case, virus could only be isolated from the cerebrospinal fluid but not from peripheral blood. Detectable viremia was transient and preceded the appearance of HIV specific antibodies. After cessation of acute symptoms, the frequency of HIV isolations was similar to that of asymptomatic carriers (23 and 26%, respectively). The role of the immune response in terminating detectable viremia remains to be established.     

A sensitive radioimmunoprecipitation assay for human immunodeficiency virus (HIV)

A sensitive and efficient radioimmunoprecipitation procedure is described which provides an alternative to Western blotting assays for characterizing antibodies directed against human immunodeficiency viruses (HIV-1). Reaction of solubilized preparations of HTLV-III with 125I-labeled Bolton-Hunter reagent leads to the efficient labeling of all of the major virus-specific proteins, including gp120, gp41, RT (p66/p51), p24, and p17. These labeled proteins are readily immunoprecipitated by immune human sera, by specific sera derived from hyperimmunized animals, and by monoclonal antibodies. This procedure, referred to as BH-RIP, provides a simple assay for characterizing and titering antibodies against HIV which is equivalent in specificity, and more sensitive and efficient than the Western blotting method. In addition, viral proteins labeled in this way are suitable for biochemical studies. In one such application, the number of high-mannose and complex oligosaccharide side chains of gp120 and gp41 were determined by examining the sensitivities of the two viral glycoproteins labeled by this procedure to the glycosidases Endo H and PNGase F.     

Slow human immunodeficiency virus (HIV) infectivity correlated with low HIV coreceptor levels

The absolute number of CD4+ lymphocytes in blood is prognostic for disease progression, yet the cell surface density of CD4 receptors or chemokine receptors on a single cell has not previously been found to be predictive of human immunodeficiency virus (HIV) infectivity outcome. It has recently been shown that human leukocyte elastase (HLE) and its ligand alpha(1) proteinase inhibitor (alpha(1)PI; alpha(1)antitrypsin) act as HIV fusion cofactors. The present study shows that decreased HIV infectivity is significantly correlated with decreased cell surface density of HLE but not with decreased CD4 nor chemokine receptors. In vitro HIV infectivity outcome in this study was predicted by the surface density of HLE on mononuclear phagocytes but not on lymphocytes. The set point HLE surface density was in part determined by alpha(1)PI. Decreased circulating alpha(1)PI was correlated with increased cell surface HLE and with increased HIV infectivity. The correlation of HIV infectivity outcome with surface HLE and circulating alpha(1)PI supports the utility of these HIV cofactors in diagnostic analysis and therapeutic intervention.     

Effect of chloroquine on human immunodeficiency virus (HIV) vertical transmission

Introduction

Over 2 million children globally are HIV positive. More than 90% are infected in utero from their mothers. Current pharmacological methods to reduce the rate of vertical transmission are too expensive for the developing world. Chloroquine, a cheap, widely available drug, has anti-HIV properties. We conducted a pilot study to determine if chloroquine can reduce HIV vertical transmission.

Methods

287 samples of stored, frozen cord blood from a cohort of Ugandan infants born to HIV positive mothers were analyzed for concentrations of chloroquine and its two major metabolites, monodesethylchloroquine and didesethylchloroquine. The HIV status of each infant was determined by ELISA with Western Blot confirmation at 15 and 18 months of age.

Results

49% of samples had measurable chloroquine or metabolite. Of those with measurable drug, the higher concentrations of chloroquine and its metabolites were more frequently associated with HIV negative infants. However, only the median concentration of didesethylochloroquine was significantly higher in HIV negative infants vs. HIV positive infants (1.6ng/ml vs. 0.9ng/ml, p=0.05).

Conclusions

Nearly half of all infants in a Ugandan cohort are exposed to chloroquine in the last trimester of pregnancy. Such random maternal chloroquine use may be associated with a decreased rate of HIV vertical transmission. The issue of maternal chloroquine use requires controlled study before any clinical conclusions may be drawn.

Funding

This work was supported by an AIDS International Training and Research Program at Case Western Reserve University (TW00011) Fogarty Grant     

Evidence for a Euro-American origin of human immunodeficiency virus (HIV)

Recent reports of the nonspecificity of the enzyme-linked immunosorbent assay (ELISA) test in African populations, significant genomic differences between simian T-cell lymphotropic virus and human immunodeficiency virus (HIV), and the early appearance of clinical acquired immunodeficiency syndroME (AIDS) in the US and Europe are powerful arguments against the assumption that AIDS originated in Africa. The authors postulate that HIV infection has been endemic in the Euro-American population at least since the beginning of the 20th century and that sociocultural changes led to the introduction of the virus into Africa. A search of the literature reveals 28 cases of disseminated Kaposi's sarcoma in the pre-epidemic 1902-66 period. In none of these cases are notations made on intravenous drug abuse, homosexuality, or other risk factors for AIDS. The majority of cases involved men, however. It is pointed out that, in a population where the incidence of a virus such as HIV is low, the number of sexual partners is limited, and intravenous drug abuse is nonexistent, an infection with as long a latency period as HIV may not only be expressed sporadically, but would probably not be recognized as a transmissible infection. On the other hand, the significant changes in these social factors that occurred as a result of the sexual revolution of the late 1960s and early 1970s would be expected to increase the spread of infection and clinical disease so that recognition would be achieved. During the past decade, there have been marked increases in the number of sexually transmitted infections in the homosexual male population. The efficiency of anal intercourse as a mode of transmission probably accounts for the fact that HIV infection first expressed itself in this population.     

Electron microscopic detection of human parvovirus (B19) in a patient with HIV infection

We report the findings on an HIV-positive patient found to be infected with human parvovirus B19. In a comparative study of sequential sera, direct electron microscopy (EM) had the same sensitivity as DNA hydridization for the detection of the virus. EM did not require specific reagents and also yielded information on the state of the virus; i.e., whether random or complexed, and the type of antibody involved. The presence of parvovirus complicated the judgement as to drug treatment. This case also highlighted the importance of diagnosing the presence of opportunistic viral infections that have no, or low-grade, pathogenic activity.     

Interaction with human immunodeficiency virus (HIV) type 2 predicts HIV type 1 genotype

In West Africa, India, and certain regions of Europe, both human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2) are known to cocirculate. To investigate the HIV-1 subtypes involved in dual HIV-1 and HIV-2 infections, we sequenced the envelope C2-V3 region from 29 dually infected female commercial sex workers from Senegal. The majority of women (23 of 29) were infected by HIV-1 subtype A. Within the HIV-1 subtype A sequences, 14 of 23 (60.8%) clustered with the West African associated A/G recombinant form (IbNG), and 9 of 23 (39.2%) formed a separate cluster distinct from the A/G IbNG. In contrast, in HIV-1 singly infected individuals, non-IbNG subtype A was found in only 13 of 98 (13.3%). Therefore, the lack of protection and/or interaction with HIV-2 was associated with a distinct HIV-1 A genotype. These results suggest differences in the biological properties of HIV-1 genotypes and their in vivo interaction with HIV-2.