A case is reported of a woman who was exposed to human immunodeficiency virus through self-insemination. She was artificially inseminated with fresh semen obtained from a gay man in whom HIV seroconversion was taking place. Postexposure prophylaxis with antiretrovirals was initiated 10 days later, and despite successful conception, HIV infection was not established. A healthy male infant was subsequently delivered with no obvious toxicity related to medication.

BackgroundEnterocytozoon bieneusi and Cryptosporidium parvum cause chronic antimicrobial-resistant gastrointestinal infections in HIV-1-infected individuals. HIV-1 reverse transcriptase inhibitors delay the onset of opportunistic infections, but are not known to reverse established infections. HIV-1 protease inhibitors are more effective across a broader range of HIV-1-infected immune cells. Combination antiretroviral therapy that includes a protease inhibitor could improve immunity to E bieneusi and C parvum.MethodsHIV-1 infected patients with chronic microsporidiosis (five), cryptosporidiosis (three), or dual infection (one), were treated with combination therapy that included at least one HIV-1 protease inhibitor. Outcome measures were symptoms, weight, use of antidiarrhoeal and antimicrobial drugs, T-lymphocyte subsets, HIV-1 viraemia, stool microscopy, and biopsy by endoscopy.FindingsAll patients had complete clinical responses, gained a median 15 kg in weight, and ceased all antidiarrhoeal and antimicrobial therapies. Biliary cryptosporidiosis responded in both affected patients. Neither pathogen was detected in follow-up stool microscopy (eight of eight patients) or in biopsy samples by endoscopy (five of five). Intestinal architecture returned to normal in three patients. There was a dense CD8 lymphocyte and macrophage infiltrate and staining of intraepithelial E bieneusi with interferon-γ before and after treatment, but little staining for CD4 or B lymphocytes, interleukin 10, or HIV-1 gp41. Five patients remained symptom-free after a median 13 months' follow-up. Four patients had recurrent diarrhoea at 7–13 months (one with positive stool microscopy), associated with declining CD4 counts.InterpretationCombination antiretroviral therapy that includes a protease inhibitor can restore immunity to E bieneusi or C parvum in HIV-1 infected individuals, and result in complete clinical, microbiological, and histological responses. The persistent CD8 cell and macrophage infiltrate, and the rapid time to relapse in patients with declining CD4 lymphocyte counts, suggest that neither infection was eradicated.

SummaryThe objective of this study was to assess the ability of HIV‐1 to establish an in vitro infection of primary human umbilical vein endothelial cells (HUVEC). The HUVEC and colon carcinoma cell lines were inoculated with different isolates of HIV‐1 (HIV‐1SF2, HIV‐1McK and HIV‐1LAI) and productive viral infection was assessed by both the detection of p24 core antigen in the culture supernatants and the presence of specific spliced HIV mRNA. The infection which was detected in the inoculated HUVEC and all the colon carcinoma cell lines could not be blocked using an antibody targeted against the CD4 receptor. Furthermore, the HIV‐inoculated HUVEC secreted elevated levels of IL‐6 and this increase was found to be proportional to the size of the viral inoculum. No changes in the production of IL‐lβ, TNF‐α, IFN‐α and IFN‐γ were detected following HIV infection. The colon carcinoma cells, however, did not secrete increased levels of these cytokines following HIV‐1 inoculation. These results confirm that non‐CD4 expressing cells, such as endothelial cells and certain colon epithelial cells, serve as targets and reservoirs for HIV. Moreover, the production of IL‐6 by HIV‐infected endothelial cells may be a contributing factor to the aberrant immunoregulation associated with HIV infection in vivo.

The pathogenesis of drug hypersensitivity in patients with HIV infection is unknown. To study further the nature of hypersensitivity, the histopathological features of morbilliform drug hypersensitivity reactions were examined in a group of HIV-infected patients. Skin sections from 23 HIV-infected subjects with morbilliform drug hypersensitivity reactions were examined by light microscopy, direct immunofluorescence and immunohistochemistry, to determine the nature of the inflammatory infiltrate and the role of immunoglobulin, complement and cytokines. The principal light microscopic findings were spongiosis, hydropic generation of the basal layer, civatte bodies, an epidermal lymphocytic infiltrate (48%), and a perivascular dermal infiltrate of lymphocytes (87%) and macrophages (52%). Two patients had findings consistent with toxic epidermal necrolysis. Immunohistochemistry demonstrated that the lymphocytic infiltrate consisted of CD8(+), HLA-DR(+) T lymphocytes (some of which also stained for CD38), a marked depletion of epidermal Langerhans cells (90%), and strong cytoplasmic staining of keratinocytes for IL-6 (60%), IL-1 beta (50%), tumour necrosis factor-alpha (TNF-alpha) (45%) and to a lesser degree, interferon-gamma (IFN-gamma) (35%). Immunofluorescence did not demonstrate any significant deposition of immunoglobulin or complement. The histological findings were independent of the responsible drug, the duration of either therapy or the rash, and of peripheral blood CD4(+) and CD8(+) cell counts. These findings suggest that activated CD8(+) lymphocytes and perhaps epidermal production of cytokines are involved in the pathogenesis of cutaneous drug hypersensitivity in HIV-infected patients. The common histological features, regardless of the causative drug, suggest a common pathogenesis.

Epstein-Barr virus (EBV) has been associated with Hodgkin‧s disease (HD) in up to 50% of cases, but the subtype of EBV involved has only recently been studied. In this report, biopsy samples from 30 patients with HD were assessed for EBV sequences using both the polymerase chain reaction (PCR) and in situ hybridization (ISH). EBV sequences were localized to the malignant Reed-Sternberg cells and their mononuclear variants (Hodgkin's cells) in 9 of the 30 cases, with 7 demonstrating A- type and 2 B-type EBV sequences. Both of the patients with B-type EBV- associated HD had features to suggest pre-existing immune compromise: one was infected with human immunodeficiency virus (HIV) and had severe CD4+ T-lymphocyte depletion; the other was a debilitated elderly patient with dementia. A previous study suggested that A-type EBV alone is associated with HD and the finding of predominantly A-type EBV in the present series is in keeping with this report. The presence of B- type EBV in the HD of patients with pre-existing immunodeficiency, taken together with the recent report that B-type EBV occurs in HIV- associated non-Hodgkin‧s lymphoma, suggests that B-type EBV may be an important human pathogen in immunocompromised patients.

Objective: To determine whether HIV could be identified in semen samples during the first few weeks after infection.Design: A series of three homosexual men with symptomatic primary HIV-1 infection.Methods: Each subject provided a series of semen samples that was examined for HIV-1 by virus culture, polymerase chain reaction (PCR) and transmission electron micrography.Results: The first samples obtained for each subject (17, 22 and 24 days following onset of primary HIV-1 infection) were all positive by PCR and negative by viral culture. Of 13 samples obtained during the first 80 days after onset of primary HIV-1 infection and analysed by PCR, 10 were positive. Only one of these samples was virus culture-positive. Four semen samples obtained from two subjects during treatment with zidovudine were PCR-positive. Eight samples were examined for presence of HIV-1 by electron microscopy and one was found to be positive.Conclusions: These results indicate that men with HIV-1 infection are potentially infectious through sexual transmission during the first few weeks after infection. The findings emphasize that individuals in all stages of HIV-1 infection should practise safer sex to reduce transmission of HIV-1.

We describe the establishment of four continuous cell cultures isolated from pleural or peritoneal fluid of patients with Kaposi sarcoma (KS) and show evidence that these cells are derived from vascular endothelium. Although provision of an extracellular matrix (fibronectin, laminin, or matrigel) was essential, the cell cultures were not dependent on exogenously added growth factors (platelet-derived growth factor, epidermal growth factor with or without heparin) for continuous culture. Specific staining for endothelial cell (EC) markers (factor VIII, Ulex europaeus type 1 lectin) and the secretion of endothelin, a vascular EC product, were demonstrated. The KS cells secreted large amounts of cytokines (granulocyte-macrophage-CSF, TNF-alpha, IL-1 beta, and especially IL-6). Conditioned media from the KS cells caused normal capillary EC to proliferate. The KS cells synthesized fibroblast growth activity in amounts sufficient to induce the proliferation of normal EC and fibroblasts. These data support the existence of a paracrine pathway of EC proliferation in KS and suggest that KS cells could sustain their own growth via an autocrine mechanism.

Mononuclear cell subpopulations present in the skin of 36 recipients of HLA‐identical sibling marrow transplants were defined by immunoperoxidase using a battery of monoclonal antibodies to cell surface differentiation antigens. The T4‐positive (T4+) (helper‐inducer T cells), T8+ (cytotoxic‐suppressor T cells) and the T6+ (Langerhans cells) decreased in number early post transplant and returned towards normal numbers from day 42 onwards. There was no evidence that either the T4+ or the T8+ subset was involved in cell‐to‐cell contact damage in acute graft‐versus‐host disease (GVHD). The paucity of lymphoid cell infiltration of the epidermis in acute GVHD suggested the possibility of a soluble factor being responsible for basal layer damage. In patients with chronic GVHD there was no evidence of T4+ lymphocyte involvement, but T8+ lymphocytes were present in increased numbers, suggesting a role for the T8+ population in the skin lesions of chronic GVHD, or possibly a reflection of the pattern of T4+ and T8+ cell reconstitution in the blood post‐transplant. Finally, our study provided no evidence that B1+ (B cells), Leu 7+ (natural killer cells), OKM1+(histiocytes) or OKT10+ cells were involved in cell‐to‐cell contact damage in either acute or chronic GVHD.

S ummary The pathogenesis of atopic dermatitis remains uncertain. The aim of this study was to correlate blood and skin findings with respect to analysis of immunoregulatory T cells in 18 patients with severe atopic dermatitis. Circulating T lymphocytes were characterised by flow cytometry, and in situ infiltrates of acute skin lesions identified by the immunoperoxidase technique. Analysis of peripheral blood T lymphocyte sub‐sets failed to reveal any difference from normal controls. Skin infiltrates were strongly positive for T11 – the pan T lymphocyte marker. The majority of these cells both in the dermis and epidermis were of the T4 helper‐inducer sub‐set, while a smaller proportion of cells were of the T8 suppressor‐ cytotoxic T cell sub‐set. T6 positive Langerhans cells were markedly increased in the dermis of affected skin, compared with normal skin. The finding of increased numbers of helper‐inducer T lymphocytes' in association with increased numbers of Langerhans cells, which function as antigen presenting cells, suggests a strong immunological mechanism in disease pathogenesis, and may yield knowledge both with respect to origin of skin damage and elevation of IgE.