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Dendritic cells (DC) are required to initiate primary cellular immune responses. Human immunodeficiency virus type 1 (HIV-1) infection of DC may be central to transmission and persistence of virus and in the pathogenesis of AIDS. In symptomatic HIV-1-infected patients the proportion of DC in the mononuclear cell population was reduced. Provirus load in the T cells was 3-100 times higher than in DC and there was no correlation between the levels of infection in the two cell types. Phylogenetic analysis of amino acids in the V3 loop and flanking regions indicated intermingling of sequences and thus provides the first evidence for transfer of virus between DC and T cells in vivo. In one of three patients analysed there were significant differences in amino acid residues in the V3 region. This may reflect reduced interactions between DC and T cells in infected individuals and for the existence of variants with a stronger tropism for DC, which could play a role in transmission by initiating infection in mucosal DC.

Immunological monitoring of disease progression following HIV infection and seroconversion illness, latency and AIDS, not only helps in the basic investigation of the natural history of the viral infection in man, but also can assist in prognosis and treatment of AIDS-defining illnesses. However, outside clinical trials, these tests should be selected and used in clinical practice only if they are validated as relevant and effective. The absolute CD4+ T-helper lymphocyte count, measured by flow cytometry, has emerged as the best available investigation, but needs care in sampling due to diurnal and circadian rhythms, effects of age, pregnancy, therapy, intercurrent infections and technique. Sampling should provide a baseline and trends-monthly intervals initially, then quarterly in uncomplicated cases. Thresholds may be given for counts (e.g. 200/microliter) below which prophylaxis against pneumocystis pneumonia should be administered, and repeating persistently low counts (e.g. below 50/microliter) is seldom helpful in practice. Serum levels of beta-2 microglobulin, neopterin and immunoglobulins rarely add information. Physicians and laboratories should have testing guidelines based on clinical audit of best practice, based in turn on scientific understanding of the immunological processes involved.

In this pilot study, the numbers of dendritic cells (DC) in peripheral blood of AIDS patients and the level of infection with HIV1 were determined before and after AZT treatment. Mononuclear cells were cultured overnight and DC were identified by their lack of labelling with antibodies specific for T, B and natural killer (NK) cells and monocytes and by their high level of staining with antibodies for MHC class II molecules. Although the numbers of DC identified by this method were lower than those identified morphologically in earlier studies (Macatonia et al., 1990), the numbers in three untreated AIDS patients were below the range seen in normals. There was also a marked rise in DC number in patients given AZT therapy. In two patients, there was a significant provirus load in the DCs which was decreased two to three weeks after the commencement of AZT therapy. The studies suggest that DC numbers and their infection levels may be markers of disease in HIV infection.

A key factor causing immunodeficiency in HIV infection seems to be defective antigen presentation. Consequently, CD4+ T-cell populations, initially those expressing CD45RO, decrease in number not because of their destruction, but because they fail to expand in response to antigenic stimulation. This view implies that it would be mistaken to aim therapies only at correcting T-cell function or preventing infection of T cells.

Factors determining the outcome of an episode of Pneumocystis carinii pneumonia (PCP) in 149 AIDS patients treated at St Mary's Hospital were identified and their importance on improved survival evaluated between 1984 and 1989. The proportion of fatal episodes of PCP decreased over time. Fatal compared with nonfatal episodes had lower mean alveolar-arterial oxygen gradient (82.5 mmHg vs 53.8 mmHg, P less than 0.001), mean haemoglobin level (11.2 g/dl vs 12.1 g/dl, P = 0.01), mean lymphocyte count (0.68 x 10(9)/l vs 0.92 x 10(9)/l, P = 0.05) and more coinfections (31% vs 5%, P less than 0.001). Over time, the most significant change which occurred was a reduction in alveolar-arterial oxygen gradient at time of first presentation with PCP (r = -0.37, P less than 0.001). Mean alveolar-arterial oxygen gradient declined from 79.9 mmHg in 1984 to 45.3 mmHg in 1989 (r = -0.88, P = 0.02), independently of zidovudine therapy or PCP prophylaxis. Patients were being treated at an earlier stage in their disease course as indicated by their reduced alveolar arterial oxygen gradient. This is due either to earlier patient presentation, earlier medical diagnosis or both. The widespread introduction of zidovudine and PCP prophylaxis may further contribute to improve morbidity and mortality patterns in the future.

Epstein-Barr virus (EBV) associated ulceration has not previously been included in the differential diagnosis of oesophageal ulcers in AIDS. We report five cases of oesophageal ulceration in homosexual men with advanced human immunodeficiency virus infection in whom this was considered to be the most likely cause. DNA in situ hybridisation studies showed EBV in biopsy material from three of four patients with oesophageal ulcers and in none of three controls. Of other viruses studied, only human papillomavirus was present, and this was found in both patients and control subjects. These findings support the hypothesis that EBV is an aetiological factor in some cases of AIDS-associated oesophageal ulceration.

Of 207 homosexual or bisexual patients with the acquired immune deficiency syndrome (AIDS), 24 with the AIDS related complex, and 39 with asymptomatic HIV infection, 32 patients were found to have mycobacterial infection. Mycobacterium tuberculosis was found in 13 patients with AIDS and in two with the AIDS related complex. M avium-intracellulare was found in 15 patients with AIDS and was disseminated in 12. One patient was infected with M kansasii and one with M ulcerans. Invasive procedures were frequently required to obtain positive bacteriological results. Subclinical carriage of M avium-intracellulare and other mycobacteria thought to be nonpathogenic was common in patients seronegative for the human immunodeficiency virus and at all stages of human immunodeficiency virus infection. All but one isolate of M tuberculosis were fully sensitive to standard antimycobacterial antibiotics. Response to treatment was usually rapid. M avium-intracellulare isolates were all resistant to first line agents in vitro, and antibiotics such as ansamycin and amikacin were required to obtain a clinical response.

Total immunoglobulin (Ig) and IgG subclass levels were measured in 72 patients with AIDS or AIDS-related complex (ARC). IgG2 subclass levels were found to be significantly decreased in the AIDS/ARC patients with pyogenic infections compared with both similar individuals without bacterial disease and the HIV-negative control group.

In a study of treatment by zidovudine in 106 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex, an acute meningo-encephalitic illness developed in 4 of 21 patients within 17 days after the dose of zidovudine had had to be reduced because of myelotoxicity. 3 of the 4 patients had previous clinical evidence of HIV encephalopathy. AIDS-related opportunist infection of the central nervous system was excluded. This acute meningo-encephalitic illness probably results from an increase in HIV replication following dose reduction.

We have treated 113 patients with zidovudine since its licensure, 80 with acquired immunodeficiency syndrome and 33 with acquired immunodeficiency syndrome-related complex. This paper reports on the efficacy and toxicity observed in these patients. Improved well-being, reduced frequency and severity of opportunist infections were notable in the first year of follow-up. More rapid improvement in pulmonary physiological tests during recovery from Pneumocystis carinii pneumonia was also observed in treated patients. Patients with lower initial platelet counts showed early increases in platelet counts. There was a consistent fall in human immunodeficiency virus (HIV) p24 antigen during treatment, although not always to undetectable levels. CD4 cell counts showed a rise in the first months of treatment but these were not sustained, despite continuing clinical benefit. Neuropsychological and clinical evidence of benefit in HIV encephalopathy are described. We have analysed the factors influencing marrow toxicity and have found that low CD4 count and the intercurrent use of ganciclovir and dapsone increase myelotoxicity. We describe the clinical and biochemical features of the myopathy associated with long-term use of zidovudine and summarise our findings on dose-reduction associated meningo-encephalitis.

Cryptosporidial infection is one of the recognised causes of diarrhoea in AIDS patients. It may also produce biliary tract disease. Fifteen out of 250 (6%) AIDS patients seen at our hospital had Cryptosporidial enteritis and five of the 15 (2% total) had clinical evidence of biliary tract disease. The radiological findings in these five patients are presented. Ultrasound examination of all five patients showed abnormalities in the biliary tree; five had dilatation and irregularity of the intra- and extrahepatic bile ducts with focal strictures, four had gall-bladder wall thickening, two had thickening of the common bile duct wall, two patients showed areas of increased reflectivity in the periductal regions of the liver and two had pancreatic duct dilatation. ERCP in one patient confirmed the ultrasound findings and Cryptosporidium oocytes were isolated from the collected bile. We conclude that Cryptosporidial infection in the biliary tree can produce distinctive appearances on ultrasound which may well obviate the need for more invasive investigations such as ERCP.

The antigen-specific immune response in HIV sero-positive individuals is depressed or absent. This may be due in part to abnormal co-operation between T lymphocytes and antigen presenting cells (APC). We have isolated from the peripheral blood of healthy heterosexuals and patients with persistent generalized lymphadenopathy (PGL) and AIDS, cells of low density (LDC) with dendritic morphology. These cells are known to be potent APC. The expression of two cell surface antigens on these cells, namely 63D3 (a monocyte related antigen) and Class II antigens was examined. LDC from controls and patients with benign, non-progressive PGL (type A) were found to show biphasic expression of Class II antigens. By contrast, the high intensity Class II expression seen on a small proportion of 63D3 negative cells from controls and patients with PGL type A was absent in patients with PGL type B (showing subtle signs of progressive immunodeficiency) and AIDS. The loss of this population of dendritic cells was reflected in the absence of stimulator activity in autologous and heterologous mixed lymphocyte reactions. Thus, it is possible that the loss of these dendritic cells may contribute to the profound immunological abnormalities seen in AIDS.