Johannes Gaub

T-cell subset alterations and lymphocyte responsiveness to mitogens and antigen during severe primary infection with HIV: a case series of seven consecutive HIV seroconverters.

Seven consecutive patients who presented with a severe acute mononucleosis-like illness associated with HIV seroconversion were evaluated by T-cell subset enumerations and measurements of lymphocyte transformation responses to mitogens and antigen during both their primary illness and a 1-year follow-up period. We observed a characteristic pattern of response to primary HIV infection; initial lymphopenia was followed by CD8 lymphocytosis and inversion of the CD4:CD8 ratio. During follow-up, the CD8 count gradually returned to normal, whereas the CD4:CD8 ratio remained inverted because of a relatively low number of CD4 lymphocytes. Primary infection was followed by prolonged and severe cellular hyporesponsiveness to both mitogens and antigen. At the last follow-up, responses to pokeweed mitogen were still severely impaired, with a median 19% (range 7-50%) of that observed in healthy controls. We conclude that severe primary HIV infection may be followed by sustained lymphocyte hyporesponsiveness, a sustained low percentage of CD4 lymphocytes and sustained inversion of the CD4:CD8 ratio.

Prognostic value of immunologic abnormalities and HIV antigenemia in asymptomatic HIV-infected individuals: proposal of immunologic staging

The prognostic value of various immunologic tests was investigated in 150 HIV-seropositive homosexual men, who were initially without HIV-related symptoms or AIDS and who were followed for a median of 12 months (range 3-28 months). The laboratory investigations included HIV antigen in serum, total lymphocyte count, T-helper (CD4) and T-cytotoxic/suppressor (CD8) counts, and lymphocyte transformation responses to the mitogens phytohemagglutinin (PHA) and pokeweed mitogen (PWM), and to antigenic extracts from Candida albicans and cytomegalovirus. 24 individuals developed HIV-related symptoms or AIDS (11 cases). All parameters except the CD8 count were of prognostic value, but a multivariate analysis of symptom-free survival showed that HIV antigenemia, a CD4 count less than 0.5 x 10(9)/l, and relative response to PWM below 25% of controls contained all the prognostic information. Individuals abnormal at entry for these 3 variables had a theoretical 36 times as high hazard of developing symptoms within the observation period as had individuals with normal parameters. There was no significant covariation between HIV antigenemia on the one hand and CD4 count and response to PWM on the other. Although, the latter 2 variables covaried, each of them provided independent information, and both were used to classify the degree of the immunodeficiency in 3 stages: Im-0 with normal values, Im-1 with one, and Im-2 with both tests abnormal. Individuals in stage Im-2 had a 10 times increased risk of developing symptoms. The immunologic staging correlated significantly with the clinical grouping (CDC criteria). This staging improved in only 1, but deteriorated in half of 36 individuals observed for at least 18 months. Thus, the staging is likely to prove useful when attempts to arrest the immunodeficiency of HIV-infected individuals has to be monitored.

The Immunological and Clinical Outcome of HIV Infection: 31 Months of Follow-up in a Cohort of Homosexual Men

T-cell subsets, antibodies (Ab) against human immunodeficiency virus (HIV) and clinical status were evaluated during a 31 (24-35) month follow-up study of homosexual men. The study group included 50 homosexual men, with many sexual partners, who by 1982-83 were without symptoms and had a prevalence of HIV Ab of 38%. Among the men who were seropositive on the initial investigation a significant decrease occurred in the absolute number of CD4+ lymphocytes (p less than 0.01). 88% of these men experienced a decrease, and by follow-up 59% had CD4+ lymphocytes below the normal range. Also the men who seroconverted during the study had a significant decrease in CD4+ lymphocytes, while no changes were observed in the seronegative group. None of the subgroups had significant changes in CD8+ lymphocyte number. AIDS or AIDS related complex developed in 33% of the men seropositive at inclusion. None of these clinical syndromes developed in the seroconverting or the seronegative group. The men who eventually developed clinical symptoms did not differ significantly from the healthy HIV Ab positive persons, with respect to lifestyle parameters, presence of lymphadenopathy and isolation of cytomegalovirus. However, they had significantly lower CD4+ cells and CD4/CD8 ratio (p less than 0.01) at inclusion. It is concluded that in the majority of persons infected with HIV, phenotypic T-cell alterations will occur with a latency of years, but it remains to be seen if the alterations necessarily will result in clinical manifestations. Further, T-cell subset determination among healthy HIV Ab positive persons will provide prognostic information.

Cytophotometry of liver cells from ethanol-fed rats: ethanol causes increased polyploidization and protein accumulation.

Abstract. Cellular protein and DNA content were determined by Feulgen‐Naphthol Yellow S cytophotometry on isolated liver cells from rats fed ethanol for 2–6 months. It was found that the parenchymal liver cells after ethanol feeding contained 13% more protein than cells of the same ploidy class from controls; that the average parenchymal cell in ethanol‐fed rats contained 16% more protein than in controls due to the increased occurrence of polypoloid cells; that the protein accumulation develops over 2 months, does not progress thereafter and disappears after a few days of reduced ethanol intake; that the tendency to form polyploid cells is accentuated during liver regeneration.

The development of AIDS or AIDS‐related conditions in a cohort of HIV antibody‐positive homosexual men during a 3‐year follow‐up period

Abstract. One hundred and thirty‐three homosexual men seropositive for the antibody against human immunodeficiency virus (HIV) were enrolled in a prospective study in 1984–85. The 3‐year cumulative incidences of the acquired immunodeficiency syndrome (AIDS) and AIDS‐related conditions, by life‐table analyses, were 18% and 34%. The cumulative incidence of immune deficiency defined as CD4 lymphocytes < 0.5 times 109 l−1 was 70% at 3 years. Absence of antibodies to p24 antigen, HIV antigenaemia, CD4 lymphocytes < 0.3 times 10 l−1 and elevated serum level of IgA were significantly associated with the development of AIDS. There was no association between disease progression and persistent generalized lymphadenopathy.

Antibody to HIV in Patients with Acute Hepatitis B in the Period 1975–1984

In order to elucidate the time when HIV was introduced into a population of patients with acute hepatitis B, serum samples collected in the period 1975-1984 from 331 patients with hepatitis B were analysed for the presence of antibody to HIV (anti-HIV). Anti-HIV was not detected in any of the serum samples from 97 females. 5/234 serum samples from males (2%) were repeatedly positive. Anti-HIV was first demonstrated in 1978, 3 years before the first patients with AIDS were recognized in Denmark. None of the 4 Danish patients with anti-HIV developed AIDS during a follow-up period of 1-7 years. However, at the time of follow-up in 1985 3 had decreased cell mediated immunity. The hepatitis B infection had an uncomplicated course in 4/5 patients with anti-HIV. One patient had a protracted delta hepatitis and was a HBsAg carrier before as well as after the acute hepatitis. Thus, the HIV infection did not cause any complicated course in this study.

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).

Efficacy and safety of two different dose levels of ganciclovir for the treatment of cytomegalovirus chorioretinitis in AIDS patients.

The effect of different dosages of ganciclovir on proved cytomegalovirus chorioretinitis was tested in a randomized trial on 11 homosexual men with AIDS. The effect of 5 mg/kg/day was as good as 10 mg/kg/day. The lower dosage had less toxicity.