Kay Ulrich

Acute HTLV III infection associated with exanthema, diagnosed by seroconversion

We report three homosexual men who developed malaise, fever and a roseola‐like exanthema which disappeared over 2 weeks. During 3 months follow‐up, all three patients felt well and had no symptoms. HTLV III seroconversion was detected several weeks after the acute HTLV III infection. In two of the three cases the Western blot technique was able to detect HTLV III antibodies before they were detectable by the ELISA technique.

Investigation of immunosuppressive properties of inactivated human immunodeficiency virus and possible neutralization of this effect by some patient sera

Retroviral infections are accompanied by immunosuppression in a variety of species. For feline leukemia virus, the immunosuppression has been ascribed to the transmembrane envelope protein, p15E, which suppresses the proliferative responses of cat, mouse, and human lymphocytes. A similar suppressive effect has been shown for a lysate of human immunodeficiency virus (HIV), strain HTLV-IIIB. Here we determined that detergent-disrupted HTLV-IIIB lystate exerted a strong suppressive effect on PHA-stimulated lymphocytes. Preparations of whole virions, a lysate of a local HIV isolate grown on MP-6 cells, and a commercially obtained UV and psoralene-inactivated lysate were examined and demonstrated to have a similar suppressive effect. The HIV lysate was not directly cytotoxic to lymphocytes and did not contain tumor necrosis factor or lymphotoxin. The HIV lysate specifically suppressed the proliferation of a range of hemopoietic cell lines from man and mouse including three EBV transformed CD4- and IL-2 receptor-negative B-cell lines. The lysate also suppressed the formation of human bone marrow colonies, whereas the lysate had only a slight or no effect on fibroblasts. The suppression of lymphocyte proliferation was not abrogated by addition of IL-2 or IL-1 and the HIV lysate inhibited the expression of IL-2 receptors on suboptimal PHA-stimulated mononuclear cells. The suppressive factor(s) has not been characterized in molecular terms, but suppressive activity was recovered in fractions with a molecular weight of about 67,000 and in both the glycoprotein fraction and in the glycoprotein-depleted fraction of the HIV lysate. Sera from one-third of a small series (N = 13) of individuals with antibodies to HIV seem to be able to neutralize the suppressive properties of HIV lysate in cultures.

Detection of antibodies to human immunodeficiency virus (HIV) in eluates from whole blood impregnated filter paper discs

A method for elution of HIV antibodies from whole blood or serum impregnated filter paper discs was developed. The results from testing of 73 eluates in an enzyme linked immunosorbent assay and the immunoblotting test agreed with the results obtained by ordinary serum testing. Significant loss of antibody activity was not observed, neither in the eluates after storage for 1 mth at -20 degrees C nor in the filter paper discs after storage for 3 mths at +4 degrees C. This technique may be useful in facilitating sample collection and transportation, particularly in remote areas of the world.

HTLV-III Antibody Testing in Three Danish Blood Banks

Abstract. The Organon Teknika Vironostika anti‐HTLV‐III/LAV test was evaluated in three Danish blood banks. The evaluation comprised in total 3,940 consecutive donors. In all three blood banks the tests were carried out exactly according to the manufacturers instructions, using a low cut‐off value defined as (4N̄ + P̄)/5, where N̄ and P̄ are means of optical densities of known negative and positive samples. By this method the overall frequency of repeatably positive samples was 0.30%. When tested by Western blot, however, none of these samples were shown to contain specific antibodies against HTLV‐III/LAV proteins. When testing different categories of patients, only sera containing HLA antibodies gave rise to false‐positive reactions. Finally, important differences in the results were observed regarding sample preparation, single or dual wavelength optical density readings, and the experience of the technical staff.

Antibodies against the major core protein p24 of human immunodeficiency virus relation to immunological clinical and prognostic findings

In 79 homosexual men positive for antibody to human immunodeficiency virus (HIV), the titer and avidity of p24 antibody was determined by an indirect ELISA and the serum tested for the presence of HIV antigen. Results were examined for a possible correlation with clinical, immunological and prognostic findings. High titers and low avidity of p24 antibodies correlated significantly with a normal pokeweed mitogen response, early lymph node changes, and an asymptomatic and stable clinical condition. In HIV antigen negative patients, low titers and high avidity of p24 antibodies correlated significantly with a progressive clinical condition. The finding of primarily high avidity antibodies against p24 antigen in patients with more advanced immunodeficiency indicates that a decline of p24 antibodies during the clinical course of HIV infection may not be explained exclusively by an increased production of viral proteins.

Serological response in patients with chronic asymptomatic human immunodeficiency virus infection

To examine a possible relationship between decreased immune function and serological parameters, such as human immunodeficiency virus (HIV) antigenaemia and the quality and quantity of whole virus antibodies and antibodies against the major core protein p24, we investigated 160 healthy HIV infected individuals (CDC classification II and III). According to the number of T-helper lymphocytes (CD4 cells) these were divided into two groups (CD4 cell counts above or below 500/µl), which according to the lymphocyte transformation response to pokeweed mitogen (response above or below 20% of control value) were further subdivided into two groups. Both the presence of HIV antigen (p=0.022) and the absence of p24 antibodies (p=0.001) correlated to a decreased CD4 cell count. Lack of p24 antibodies was more frequent than was the presence of HIV antigen among persons with decreased CD4 cell count and decreased response to pokeweed mitogen, indicating that absence of p24 antibodies may be an earlier marker of immune dysfunction than the presence of HIV antigen. In persons with p24 antibodies present, a low such titer was associated with a decrease of both immune parameters. Presence of HIV antigen and absence of p24 antibodies thus seems to correlate with the severity of immune dysfunction in healthy HIV infected individuals.

A comparison of three methods for detection of antibodies against the major core protein p24 of human immunodeficiency virus

The native major core protein p24 of the human immunodeficiency virus (HIV) was immunoaffinity purified by a monoclonal antibody and used to develop an indirect enzyme-linked immunosorbent assay (inELISA) for detecting p24 antibodies in human sera. Its ability to detect p24 antibodies was compared to that of the immunoblotting test (IBT) and a commercial available competition ELISA (compELISA) employing recombinant HIV core protein. In tests on 60 serum samples the overall agreement of the inELISA and the IBT was 93.3%. Fifty-two samples were p24 antibody positive in both the inELISA and the IBT and of these 24 (46.2%) were positive in the compELISA. All compELISA positive samples were derived from healthy individuals, whereas of the 28 (53.8%) compELISA negative samples 1 was from a patient with acute HIV infection, 18 from healthy individuals and 9 from ARC/AIDS patients. The compELISA was able to distinguish among healthy persons with normal or low T-helper cell count (P = 0.048), as was the inELISA when p24 antibodies were titrated (P = 0.027). The inELISA equals IBT in specificity and sensitivity, is convenient and is very suitable for titration of p24 antibodies.

HIV Neutralizing Antibodies: Development and Association with HIV Related Disease

Serum neutralization was measured in 72 sera collected during a 5.5-year period from 10 HIV infected individuals. Neutralizing antibodies (NA) were present in all sera. NA titers ranging from greater than 40 to greater than 640 were detected in sera from 4 patients, who all remained healthy and further an increase with time of NA was observed in these 4 patients. Progression to disease was observed in 3 persons with NA titers less than or equal to 40 who also lacked or lost anti-gag antibodies. Two of these patients were HIV antigenaemic prior to development of disease, whereas antigen was not detected in the remaining 7 healthy persons. A weak positive correlation (R(S) = +0.643, p less than 0.001) was found between titers of NA and whole virus antibody (WVA), with the ratios between titers (NA titer/WVA titer) varying a 100-fold. The results suggest that the presence of NA in some cases might be related to a healthy carrier state and that a combination of low titer NA with decline of anti-gag antibodies and/or HIV antigenaemia is associated with progression to clinical disease.

Serological Markers of Primary HIV Infection

39 persons with an incidentally discovered seroconversion from HIV antibody negative (Ab-) to antibody positive (Ab+) state as measured by an enzyme-linked immunosorbent assay (ELISA) were investigated for the presence of (1) HIV antigen (Ag) and (2) immunoblotting test (IBT) Ab in serum samples collected within the year before seroconversion. 13 (33%) of the patients were HIV Ag+ at some time before seroconversion. However, the collection of samples was not done systematically and the samples from patients who had at least 1 sample collected within 3 months before seroconversion were thus compiled separately. This group consisted of 58 samples from 19 patients and among these none were HIV Ag+ earlier than 11 weeks before seroconversion, but the prevalence of HIV Ag+ samples was rising towards seroconversion and 10 patients (53%, 95% confidence limits: 29-76%) became HIV Ag+ in this 11-week period. Further, among all patients 13 (33%) were IBT Ab+ 4-50 days (median: 14 days) before seroconversion. Finally, among 18 patients with signs and symptoms consistent with an acute HIV infection 10 were HIV Ag+, as opposed to 4 HIV Ag+ patients among 21 without symptoms (p = 0.041).