Splenectomy in patients with AIDS and AIDS-related complex.

OBJECTIVE: To study the effect of splenectomy in HIV-infected patients. DESIGN: A retrospective chart review of patients admitted to St Vincent's Hospital who had splenectomies and were HIV-positive. SETTING: All patients were treated at St Vincent's Hospital, New York City, New York, USA. PATIENTS: Only patients who were HIV-positive and who had had a splenectomy at St Vincent's Hospital were included. INTERVENTION: All patients had a splenectomy. MAIN OUTCOME MEASURES: The effect of the splenectomy in these HIV-positive patients was studied with respect to their operative morbidity and mortality, platelet counts, overall survival and the development of new opportunistic infections. RESULTS: All patients who did not have AIDS but did have thrombocytopenia responded to splenectomy in terms of their thrombocytopenia. None of them had an accelerated progression to AIDS. Most patients with AIDS and thrombocytopenia responded to splenectomy in terms of correcting their thrombocytopenia. CONCLUSIONS: Splenectomy as a treatment for thrombocytopenia is successful not only in HIV-positive patients without AIDS, but also in AIDS patients. However, in patients with disseminated Kaposi's sarcoma or Mycobacterium avium intracellulare, splenectomy may not be a factor for survival.

Extracorporeal photopheresis in the treatment of AIDS-related complex: extended trial.

The objective of this study was to further evaluate the relative safety of extracorporeal photopheresis in the treatment of patients with AIDS-related complex. Twenty patients with AIDS-related complex, three from the initial report and 17 additional patients, were enrolled. The patient population had various risk factors. There were nine homosexuals, five heterosexual consorts of human immunodeficiency virus (HIV)-positive patients, four reformed i.v. drug abusers, and two hemophilia patients. The patients received monthly treatment with extracorporeal photopheresis. In 16 of the 19 patients, this study provides evidence of clinical stability over a longer period. The relative stability of beta 2-microglobulin and neopterin levels demonstrates that photopheresis therapy does not have an untoward effect on the degree of activation of the immune system with respect to induction of HIV replication. Antibody titers to the major viral antigens, envelope glycoproteins (gp) 120 and 41, reverse transcriptase enzyme gp 66/31 and 55, and the core protein p24 remained stable throughout the course of therapy. A subjective improvement was noted in the majority of patients. The evaluation of T-cell subsets revealed that the photopheresis treatment did not have a detrimental effect on CD3 and CD8 cells. Some decreases were noted in the CD4 cell counts but the decline may be less than is normally seen at corresponding stages of HIV infection. Skin test responsivity improved in 11 patients, remained unchanged in seven patients, and declined in two. The preliminary results suggest that in HIV disease, extracorporeal photopheresis is safe and warrants a prospective controlled trial.

One-year follow-up of vaccine therapy in HIV-infected immune-deficient individuals: a new strategy.

Immunization of AIDS/ARC patients with autologous cells expressing HIV antigens, although providing clinical and biological benefits, fails to restore cellular immunity. The latter result is due partly to the antiproliferative effect of HIV-1 on activated T-cells (immune suppression), which leads to blockade of specific immune reactions. To overcome immune suppression, a new vaccine strategy was designed consisting of an immunization against HIV-1 combined with components of the T-cell-suppressive (antiproliferative) network. This new vaccine treatment proved to be innocuous in mice, monkeys, and two non-HIV-infected humans. A Phase I clinical trial was performed in six patients previously under cellular immunotherapy and still presenting a cellular immune defect. Preliminary results confirmed, after a 1-year follow-up of the patients, the safety of the new vaccine, which also partially restored the cellular immune response, including anti-HIV HLA-restricted cell-mediated cytotoxicity, delayed hypersensitivity to recall antigens, and proliferation of T-cells specifically activated by recall antigens.

Pediatric acquired immunodeficiency syndrome-related complex: clinical and immunologic features.

The long term clinical outcome for infants and children with the pediatric acquired immunodeficiency syndrome-related complex is unknown. This report describes our experience with 14 patients with acquired immunodeficiency syndrome-related complex who have been followed for 11 to 71 months since the onset of their symptoms. The most frequent clinical features at presentation were persistent generalized lymphadenopathy (14 of 14), hepatosplenomegaly (11 of 14) and a history of recurrent otitis media (7 of 14). Except for hypergammaglobulinemia (14 of 14) and reversed T4/T8 ratios (9 of 14), immunologic analyses, including in vitro responses to mitogens and antibody responses following immunization, revealed no consistent abnormalities. Over the course of follow-up, none of the patients have developed serious or opportunistic infections and 12 of 14 have shown catch up or age-appropriate growth. The T4/T8 ratios have remained stable in 8 of 11 and improved in 2 of 11 patients. Gradual regression of hepatosplenomegaly and lymphadenopathy has been noted patients. Although follow-up studies over a longer period are needed to confirm our observations to date, acquired immunodeficiency syndrome-related complex may represent a prolonged plateau in the course of human immunodeficiency virus infection in many infected children. Detailed immunologic evaluation of these patients may help to identify a subset of children that could benefit from periodic gamma-globulin or chronic antibiotic therapy.

Viral-specific immunization in AIDS-related complex by photopheresis.

The potential for therapeutic intervention in 7 patients with AIDS-related complex (ARC) was evaluated through the use of photopheresis. The rationale for the study was based on: 1. the demonstration that psoralen and UVA could inactivate HIV/virus in vitro; 2. CD4 cells are the primary target population effected by HIV and photopheresis; and 3. reinfusion of inactivated virus and cell-associated virus might serve to engender an immune response. Preliminary results in 7 patients with ARC over 6 to 18 months revealed a virus-specific response with an elevation of HIV antibodies, while EBV and CMV titers remained unchanged. The immunologic results revealed an increase in the CD8 lymphocyte population, stable activation markers (B2 microglobulin neopterin), a decrease in p24 antigen titers and inability to culture HIV virus in 3 patients. All of these results were in the context of a stable or increasing CD4+ percent. Six patients did not reveal a generalized inhibition of other immune responses as demonstrated by recovery of DTH. In addition, the resolution of lymphadenopathy, night sweats, fever and weight loss, paralleled the immunologic response.

Glucan-induced keratoderma in acquired immunodeficiency syndrome.

Six of 20 patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex receiving intravenous infusions of soluble glucan (beta-1-3 polyglucose) developed a keratoderma of the palms and soles. The eruption began during the first two weeks of therapy and resolved two to four weeks after its discontinuation. The eruption was different in appearance from our previously reported keratoderma blennorrhagica in AIDS-associated psoriasis. None of the other 735 patients with AIDS or AIDS-related complex not treated with soluble glucan developed a similar keratoderma. The correlation between receiving glucan and the hyperkeratosis is highly significant. Since glucan is a naturally occurring component of the cell walls of yeast, fungus, and some bacterial organisms, recognition of its ability to induce such a striking reaction pattern may be of general significance and interest, although the reaction itself may be limited to patients with AIDS.

Acquired immunodeficiency syndrome-associated psoriasis and Reiter's syndrome.

Human immunodeficiency virus (HIV) causes a spectrum of immunodysfunction, the most severe of which is the acquired immunodeficiency syndrome (AIDS). We have followed the course of psoriasis in 13 patients over 2 1/2 years in a population of more than 1000 HIV-positive individuals. Four patients had a history of mild psoriasis that became severe and uncontrollable as symptoms of immunodeficiency developed. Psoriasis and HIV positivity, AIDS-related complex, or AIDS simultaneously developed in nine patients. In addition to psoriasis, Reiter's syndrome (arthritis, urethritis, and conjunctivitis) developed in one patient in the first group and three patients in the second group. Opportunistic infections, especially candidiasis and Staphylococcus, drugs, and an altered immune system may contribute to the development or flare of psoriasis in these patients. The appearance of severe psoriasis (especially in a patient with other risk factors for HIV) should prompt evaluation for HIV, and may be a poor prognostic indicator in HIV-positive patients, since nine of our 13 patients have died. Immunosuppressive therapy with methotrexate is contraindicated in this group of patients. Newer forms of drug therapy including etretinate show promising results for the management of AIDS-associated psoriasis.

Major salivary gland lymphoepithelial lesions and the acquired immunodeficiency syndrome.

Presently, there is no consensus regarding the most appropriate diagnostic and therapeutic approach to patients with human immunodeficiency virus (HIV)-associated lymphoepithelial lesions of the major salivary glands. A retrospective review of 60 consecutive patients with lymphoepithelial lesions is presented. Thirty-eight cases were associated with HIV infection. Lesions associated with HIV infection were usually bilateral, multiple, cystic, and associated with lymphadenopathy. In contrast, in those cases without HIV infection, the lesions tended to be solitary and solid. In the HIV-infected group, treatment included surgery, radiotherapy, zidovudine (AZT), and/or cyst aspiration. All therapeutic regimens, other than aspiration alone, were found to be effective. Eighteen of the patients with HIV infection developed the acquired immunodeficiency syndrome (AIDS) during the study period. Surgical treatment is probably not necessary in the majority of HIV-associated cases. Depending upon individual circumstances, treatment with AZT or low-dose radiotherapy is recommended. A diagnostic and therapeutic algorithm is presented as a guide to the management of future cases.

Value of lymph node biopsy in the treatment of patients with the human immunodeficiency virus.

The indications and value of lymph node biopsy in patients infected with the human immunodeficiency virus (HIV) are not clearly defined. We reviewed 29 consecutive lymph node biopsies performed on 24 patients with the HIV over a 4-year period. Indications for biopsy included: (1) new or worsening medical symptoms with no detectable etiology in patients with lymphadenopathy, (2) disproportionately larger or enlarging lymph node in patients with generalized adenopathy, and (3) exclusion of concomitant disease in patients with previously defined infectious or neoplastic processes. The biopsy samples exhibited a diversity of histologic appearances including atypical and reactive hyperplasia, malignancy, and infection. Nineteen biopsies (64%) resulted in the institution or alteration of treatment. The absolute number of T-helper cells prior to biopsy was significantly lower in patients with a diagnosis of malignancy or infection (p < 0.05), as well as in those who eventually died (p < 0.05). Four (14%) minor complications resulted from lymph node biopsy. Based on our results, we conclude that lymph node biopsy is indicated in the above three subsets of HIV-infected patients. Biopsy can be performed with minimal morbidity and significantly alters therapy in the majority of patients.

Whole body hyperthermia associated with beta-carotene supplementation in patients with AIDS.

The objective of this work was to check possible additive beneficial effects of whole body hyperthermia (WBH) associated with beta-carotene (BC) supplementation in patients with AIDS. In a pilot study, 10 HIV positive patients, (8 with AIDS and 2 with AIDS related complex, ARC), after AZT or DDI discontinuation, were first treated with one single session of WBH applied with a non-invasive procedure at 42 degrees C core temperature for one hour, and subsequently supplemented with BC 120 mg daily continuously. All patients well tolerated the non-invasive WBH as well as the high dose BC supplementation. Apart from one patient who died after 4 months, all the others underwent an HIV burden diminution, clinical improvement and amelioration of laboratory data, along with an subjective improvement of their life quality. With reference to control groups, namely (a) only WBH applied with extracorporeal procedure to 31 AIDS patients, and (b) only BC supplementation at high dosage applied to 64 ARC patients, the combined physical and BC supplemental treatments clearly showed a better and longer lasting response.

Nutritional support of patients with AIDS.

Investigators are now predicting that nearly 100% of the estimated 12 million HIV-positive persons in the world will develop AIDS. Most persons with AIDS will experience progressive weight loss and malnutrition prior to death. Because nutritional therapy clearly has a beneficial effect on the clinical course and immunologic status of the critically ill general population, one must not disregard its potential for benefits in the treatment of persons with AIDS. As a result of the escalating cost of medical therapy and the inevitable AIDS epidemic, the nutritional management of persons with AIDS must be simple to administer and cost effective. The author has developed nutritional screening criteria to identify those patients who would most benefit from nutritional therapy. Because these patients differ in their nutritional requirements, diet tolerance, and degree of gut dysfunction, there is no single nutritional therapy that can be used routinely to treat all malnourished persons with AIDS.

From experimental to clinical attempts in immunorestoration with bestatin and zinc.

Severe impairment of the lymphopoietic cell renewal system is an important etiological factor of cancer development and it may be the consequence of massive radio and/or chemotherapeutic regimens. In a comparative study, we analysed the potential, systemic immunorestoratory capacity of bestatin, a microbial leucil-aminopeptidase inhibitor and of the ubiquitous trace element zinc. In vivo administration of bestatin in mice stimulated both Interleukin 1 and Interleukin 2 production, and enhanced T cell, B cell as well as macrophage mediated immunoreactions. In a phase II clinical trial on 41 patients with non-Hodgkin lymphoma, Hodgkin disease and solid tumors, bestatin treatment corrected the pathological frequency of both OKT4 and OKT8 lymphocyte subpopulations. Zinc-saturated transferrin had a significative stimulatory effect on the ongoing DNA synthesis of antigen activated human lymphocytes in culture. Oral administration of zinc-gluconate to patients who manifested a severe T cell subpopulation defect corrected preferentially the OKT8 suppressor/cytotoxic T cell unbalances. The clinical results obtained by both bestatin and zinc were observed only on a short-term, so further studies are needed to elaborate long lasting regiments and to establish whether these treatments have determinant influence on the underlying disease.

New approach to treatment of AIDS and AIDS related complex.

A new approach for treatment of AIDS is suggested. This is to isolate the patient's blood, to remove anti-T-cell substance from the plasma, and treat the cells with an anti-viral agent. And then return it into the patient.

Reassessing intensive care for patients with the acquired immunodeficiency syndrome.

The number of patients with the acquired immunodeficiency syndrome (AIDS) admitted to hospitals is increasing dramatically. Treatments such as zidovudine, aerosolized pentamidine, and nutritional support are being administered to subacutely ill patients with increasing effectiveness. The number of patients with AIDS treated in intensive care units, on the other hand, has been decreasing progressively, perhaps as a result of a mortality rate close to 90%. However, because recent data demonstrate (1) a lower mortality rate in patients with AIDS who receive mechanical ventilation and (2) the ability to reverse the wasting syndrome in selected groups, we propose a reassessment of the criteria for intensive care unit admission of patients with AIDS.

Development of immunomodulators for treatment of HIV infection.

Although considerable attention has been devoted to development of antiviral drugs for therapy of HIV infection, relatively little priority has been directed to correction of the progressive immunologic defect that develops in these patients. We described the development of the therapeutic effect of an immunosupportive biological agent (IMREG-1) derived from human leukocytes. Specifically, IMREG-1 reduced the risk of progression from advanced AIDS-related complex (ARC) based on a randomized double-blinded control trial over a six month period of the laboratory and clinical parameters predictive of a high risk of progression from ARC to AIDS. The comparative value of CD4+ cell numbers, anergy to recall antigens and symptomatology in assessing risk of progression were also examined.

HTLV-III infection. A clinical approach to diagnosis and treatment of the 'AIDS virus'.

The retrovirus human T cell lymphotropic virus type III (HTLV-III) can cause no symptoms at all, a syndrome of vague symptoms such as fever and fatigue, or full-blown acquired immune deficiency syndrome (AIDS). Serologic tests for antibodies to HTLV-III are available for identifying the virus; tests for T lymphocyte subset numbers and function and white cell count are also helpful. Management of patients with the virus depends on clinical presentation: Patients who are asymptomatic carriers need only reassurance and follow-up, patients with mild illness need symptomatic treatment and monitoring, and patients with full-blown AIDS need increasing levels of physical and emotional supportive care. Through early diagnosis, treatment when needed, and patient education, primary care physicians can be instrumental in curtailing the spread of HTLV-III infection.

[The in vitro potentiation of LAK cell cytotoxicity in cancer and aids patients induced by F3--a fractionated extract of Astragalus membranaceus].

The in vitro induction of LAK cell activity was studied in cancer and AIDS patients. F3, an immuno-regulatory component of Astragalus membranaceus was shown capable of potentiating the LAK cell inducing activity of rIL-2. The killing activity against Hs294T melanoma cell line of LAK cells induced by 50 U/ml rIL-2 in the presence of F3 (55 micrograms/ml) reached 64% which was comparable to that (60%) induced by 500 u/ml of rIL-2 alone. With F3 plus rIL-2, the effector to target cell ratio could be reduced to one-half in order to obtain an equivalent level of cytotoxicity when rIL-2 was used alone. In some patients, whose peripheral blood lymphocytes were relatively inert to rIL-2, F3 could make them responsive to rIL-2. These results imply that F3 may be useful to potentiate LAK cell activity, reduce the amount of rIL-2 and thus minimize the later's toxic side effects when used in vivo.

Thrombocytopaenia as the presenting feature of persistent generalised lymphadenopathy (PGL) in a one year old.

A one-year-old child who presented with thrombocytopaenia was found to be HIV positive and has now developed persistent generalised lymphadenopathy (PGL).

Thrombocytopaenia as the presenting feature of persistent generalised lymphadenopathy (PGL) in a one-year-old.

A one-year-old child who presented with thrombocytopaenia was found to be HIV positive and has now developed persistent generalised lymphadenopathy (PGL).

[Effect of alfa-2b interferon on prognostic parameters and clinical events in HIV positive patients in the LAS/ARC stage]. / Einfluss von alpha-2b-interferon auf prognostische Parameter und auf klinische Ereignisse bei HIV-positiven Patienten in den Stadien LAS/ARC.

A number of in vivo and in vitro results suggest that interferons have an antiretroviral effect on HIV. To check this, 15 HIV-positive patients who had no full-blown AIDS, were treated with recombinant interferon alpha 2b (5 mill. IU s. c. three times a week) over a period of six months. Twelve to 16 weeks after the initiation of treatment, an increase in CD 4 lymphocytes (+16%), NK cells (+16%), lymphocytes stimulation by con A (+ 176%), neopterin (+66%), and beta-2-microglobulin (+19%) was observed. By the end of the study, all these parameters had slightly decreased again. In all patients with CD4 lymphocytes greater than 0.2 c/nl, we observed a decrease in p24 antigen levels, but in patients with CD4 lymphocytes less than 0.2 c/nl, an increase. It would thus seem that any antiretroviral effect of IFN (as shown by the p24 antigen parameter) is more pronounced in patients with superior immune parameters.