AnthonyJ. Pinching

HUMAN IMMUNODEFICIENCY VIRUS INFECTION IN TWO COHORTS OF HOMOSEXUAL MEN: NEUTRALISING SERA AND ASSOCIATION OF ANTI-GAG ANTIBODY WITH PROGNOSIS

Sequential sera from 48 subjects infected with human immunodeficiency virus type I (HIV-I) were examined over 36 months for the presence of neutralising antibodies, and for specific anti-gag (p24) and anti-env (gp41) antibodies to HIV-I. Results were interpreted in terms of clinical outcome during the period 1982/3 to 1985/6. HIV-I-infected subjects who remained symptom-free, by comparison with those who manifested AIDS or AIDS-related complex (ARC), had a significantly higher titre of anti-p24 antibodies throughout the 3 years, as measured by competitive enzyme-linked immunosorbent assay and radioimmunoprecipitation. The symptomless subjects also showed a trend towards an increasing neutralising antibody titre with time. There was no relation between anti-gp41 titre and clinical outcome, nor an independent relation between anti-p24 and neutralising titre. A lower or falling titre of anti-p24 antibody was associated significantly with clinical progression, up to 27 months before development of AIDS/ARC.

PREVALENCE OF ANTIBODY TO HUMAN T-LYMPHOTROPIC VIRUS TYPE III IN AIDS AND AIDS-RISK PATIENTS IN BRITAIN

2000 persons in the UK were examined serologically for antibodies to human T-lymphotropic virus type III (HTLV-III). Sera reacting in a membrane immunofluorescence assay (IFA) to HTLV-III were also positive when tested against cells infected with lymphadenopathy virus (LAV-1), and cross-adsorption tests indicated that these retroviruses are probably identical. A competitive radioimmunoassay (RIA), which was wholly concordant with IFA, was used to screen the sera. 30/31 patients with the acquired immunodeficiency syndrome (AIDS) were seropositive, as were 89% patients with persistent generalised lymphadenopathy (PGL), 17% symptomless homosexual men, 34% haemophiliacs receiving pooled clotting factors, and 1.5% intravenous drug abusers. None of more than 1000 unselected blood donors was seropositive. These data confirm the close association between HTLV-III and AIDS and PGL and show that infection with HTLV-III is also prevalent in the populations in whom these syndromes are most likely to develop. However, it would be unwise to presume that AIDS will necessarily develop in seropositive subjects.

Immunocytochemical detection of T and B cell populations in routine blood smears.

Immunofluorescence labelling of peripheral blood mononuclear cells is usually done on cells in suspension. This paper describes a procedure based on immuno-alkaline phosphatase staining of routine blood smears. The advantages of this method are that a few drops of blood are sufficient for labelling multiple lymphocyte subpopulations; smears may be stored for long periods before labelling; it is unnecessary to isolate a mononuclear cell fraction before labelling; labelled preparations can be stored; and the morphological features of labelled cells are shown clearly. The technique was used to label T cells and their subsets, B cells, and HLA-DR antigen in blood smears from 15 normal donors, from 7 patients with infectious mononucleosis, from 1 patient with clinically proven AIDS, and from 1 symptom-free subject at risk of AIDS. The normal T helper/suppressor ratio of 1 X 95 was reversed in all of the last three groups of subjects, the mean being 0 X 34 for infectious mononucleosis; the value was 0 X 22 in the AIDS patients. Immuno-alkaline phosphatase labelling of routine blood smears seems to be a valuable method for studying abnormalities in circulating lymphocyte subpopulations and lends itself to mass screening for altered T helper and T suppressor subjects-for example, in blood donors.

STUDIES OF CELLULAR IMMUNITY IN MALE HOMOSEXUALS IN LONDON

97 symptom-free homosexuals were studied clinically, serologically, and with in-vivo and in-vitro tests of cellular immune function in the context of the acquired immunodeficiency syndrome (AIDS). A high proportion of these men showed abnormalities: lymphopenia (33%), decreased T-helper/T-suppressor (Th/Ts) cell ratios (43%), both these abnormalities (12%), decreased total T-helper cells (15%), monocyte chemotactic (10%) and phagocytic (27%) defects, anergy to three recall antigens (32%), and anergy to purified protein derivative despite BCG inoculation (55%). The lymphocyte abnormalities and anergy characteristic of AIDS were seen in 5%. No clear clinical or serological associations were seen for the AIDS-like defects. Trends of association were seen between higher lymphocyte counts, lower Th/Ts ratios, more T-suppressor cells and serological evidence of previous virus infection. The combination of lymphocyte abnormalities and anergy observed in these symptom-free homosexuals may represent a latent phase of AIDS.

Association of different allelic forms of group specific component with susceptibility to and clinical manifestation of human immunodeficiency virus infection.

The distribution of phenotypes of the group specific component (Gc) was examined in 203 homosexuals at risk of infection or infected by the human immunodeficiency virus and compared with that in 50 randomly selected homosexuals and 122 healthy male heterosexual seronegative controls. 30.2% of patients with the acquired immunodeficiency syndrome (AIDS) were homozygous for Gc 1 fast (Gc 1f) compared with 0.8% of controls (p less than 0.0001); patients with other clinical manifestations of HIV infection were also more likely than controls to have Gc 1f. By contrast, seronegative symptomless homosexual contacts of AIDS patients (AH-p) lacked this phenotype but were more likely than controls to be homozygous for Gc 2 (25% vs 9%, p less than 0.05). AIDS patients lacked the homozygous Gc 2 phenotype altogether. A chi 2 trend test showed that progression to AIDS had a strong positive association with the Gc 1f allele (p less than 0.0001) and a negative one with Gc 2 (p less than 0.05). It is proposed that Gc may be involved in viral entry into host cells, the ease of which varies with different allelic forms of Gc, according to their sialic acid content.

Longitudinal Immunological Studies on a Cohort of Initially Symptom-Free Homosexual Men in London with Respect to HTLV-III Serology

In late 1981, when AIDS was becoming increasingly well-documented in the USA, we set up a study to examine cellular immmunity in symptom-free homosexuals in London. We felt that if AIDS did not develop, it would be of interest to determine why not, since the life-style of this community was kncwn to be similar to that in New York. On the other hand, if the disease were indeed to develop, we had an important opportunity to study the background cellular immunological profile of sexually active gay men before the disease emerged; such a high-risk, low-incidence population was not as readily studied in the USA. It has since been shown that AIDS is an infectious disease caused by the novel retrovirus HTLV-III/LAV. An epidemic of this infection has occurred in the UK following that in the US by some three years. By December 1984 there had been 102 cases in the UK (35 at St Mary’s), compared with 28 at the same time in 1983 and 7 at the end of 1982. Persistent generalised lymphadenopathy (PGL) has also increased over the same period: at the Praed Street Clinic, a large clinic for sexually transmitted diseases, we had seen a total of only 7 cases in 1982, but this had risen to 47 by the end of 1983 and to 150 at the present. A recent study on the prevalence of antibodies to HTLV-III in the UK (Cheingsong-Popov et al, 1984) has shown that 17% of symptom-free homosexuals were seropositive.