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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Preclinical and clinical studies with an azidothymidine (AZT)/interferon-alpha (IFN-alpha) combination resulted in a marked and synergistic antiretroviral activity. The administration of the two drugs in HIV-seropositive patients affected with Kaposi's sarcoma, however, induced neutropenia, thrombocytopenia, and, in some cases, anemia. A possible means to improve the therapeutic index of AZT and/or IFN-alpha in AIDS patients could be the addition of hematopoietic growth factors. In vitro activity of cytokines on the hematotoxicity of the AZT-IFN-alpha association has not yet been studied. We have performed an in vitro study to evaluate the toxicity of AZT, IFN-alpha, or both on peripheral blood hematopoietic progenitors (CFU-GM and BFU-E) and to assess the activity of interleukin 1 (IL-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), or both in modifying AZT-IFN-alpha hematotoxicity. Results indicate that AZT, IFN-alpha, and combinations of the two have a dose-dependent inhibitory effect on the in vitro growth of peripheral blood hematopoietic progenitors. Combinations of AZT and IFN-alpha inhibited CFU-GM and BFU-E proliferation in an additive manner. Neither IL-1 nor GM-CSF alone was able to induce a significant reduction of AZT-induced damage. Only the addition to the cultures of both cytokines partially curbed the antiproliferative activity of AZT at low dosages.
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PMID:Azidothymidine and interferon-alpha in vitro effects on hematopoiesis: protective in vitro activity of IL-1 and GM-CSF. 749 65

Infectious complications represent significant challenges for children with cancer and those infected with HIV. Although both have similarities in the disease- and treatment-related alterations in host defences, there are significant differences that can have an impact on the approach to treatment and prevention of the dominant infectious complications. An important difference is that children with cancer readily recover from neutropenia. Thus, the immune deficits are interspersed with intervals of immunological recovery. On the other hand, children with HIV infection do not appreciably recover from the progressive, immunological changes associated with the underlying HIV infection. The loss of cellular and humoral immunity is generally not reversible, and thus the risk of infection only increases over time. Bacteria constitute the predominant pathogen for paediatric cancer patients but invasive mycoses, viruses and parasitic infections are emerging as important pathogens. In paediatric cancer patients, strategies have been directed at altering or suppressing the endogenous colonization patterns of pathogenic bacteria. The success of this approach has been limited and at the expense of selecting for antibiotic-resistant bacterial infections. Children with HIV infection are at risk of developing a wide spectrum of pathogens. Strategies for infection prevention in the HIV setting have been directed at specific organisms, generally using more specific antimicrobial agents and with greater success.
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PMID:Infection prevention strategies for children with cancer and AIDS: contrasting dilemmas. 756 Sep 51

We report three cases of zygomycosis (mucormycosis) occurring in three individuals infected with the human immunodeficiency virus (HIV) and review 12 other published cases. We present the only two case reports of disseminated zygomycosis in AIDS patients, and the only AIDS patient with renal zygomycosis to survive without nephrectomy, receiving intravenous (i.v.) amphotericin alone. Coinfection with zygomycosis and HIV is rare, occurs primarily in patients with low CD4+ lymphocyte counts, does not always require the usual predisposing conditions for zygomycosis, and may be the presenting opportunistic infection among HIV-infected persons. Transient episodes of neutropenia occurring within 4 months before presentation may be a risk factor for this disease. Zygomycosis may arise in multiple sites including the basal ganglia, cutaneous tissue, kidney, respiratory tract, and may be disseminated. Occurring more commonly in, but not restricted to, injection drug users, it is significantly associated with sites other than basal ganglia in those patients with advanced HIV disease or AIDS. The presenting symptoms are related to the site of involvement, and the illness may develop insidiously or progress rapidly to a fulminant course. Successful therapy usually consists of surgical debridement and intravenous amphotericin B. Overall mortality in this review is 40%, and is significantly associated with sites of disease inaccessible to surgical debridement.
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PMID:Zygomycosis (mucormycosis) and HIV infection: report of three cases and review. 758 40

A case of intravenous catheter-related cutaneous aspergillosis and Aspergillus fumigatus fungemia in an HIV-positive patient with Burkitt-cell acute lymphocytic leukemia is reported. The patient developed pulmonary aspergillosis with a rapidly fatal outcome despite recovery from neutropenia and improvement of the underlying malignancy. The unusual severity and rapid spread of the infection, despite normal neutrophil count and prompt antifungal therapy, suggest that HIV-related immunocompromise might play a role in the impairment of host defences against Aspergillus infection. Thus catheter-related cutaneous aspergillosis could lead to a severe deep-seated infection in HIV-positive patients.
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PMID:Catheter-related cutaneous aspergillosis complicated by fungemia and fatal pulmonary infection in an HIV-positive patient with acute lymphocytic leukemia. 758 26

This is the first report to evaluate the effects of combination chemotherapy on HIV-1 surrogate markers in an HIV-1-infected patient with an advanced epithelial ovarian cancer. Cisplatin combined with cyclophosphamide was well-tolerated, without significant changes in the HIV-1 p24 antigen, neopterin, beta 2-microglobulin, and CD4 values. The patient demonstrated a chemical and clinical response to therapy, without evidence of opportunistic infection or severe neutropenia. During the 6-month period of observation, treatment with cisplatin and cyclophosphamide did not significantly increase the risk of HIV-1 disease progression.
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PMID:Effect of combination chemotherapy with cisplatin and cyclophosphamide on human immunodeficiency virus type-1 surrogate markers in a patient with advanced epithelial ovarian cancer. 770 91

We present a retrospective analysis of 31 (30 male) patients with HIV-associated gastrointestinal lymphoma which was undertaken to determine the natural history and response to therapy. Only seven patients had stage I or II lymphoma and 22 had stage IV. Pathology included diffuse large cell (13), immunoblastic (10), and small cell non-cleaved (7). The median age at presentation was 39 years (range 24-59), and the median CD4 count before treatment was 100/microL (range 4-1150). Eighty-seven percent of patients received systemic chemotherapy and significant response was seen in 84% (CR 38%; PR 46%). Hematologic toxicity was high (febrile neutropenia in 44% and dose reductions were required in 81%) and perforation occurred in five patients. Median survival for all patients was 6 months and death was secondary to lymphoma in 61%, treatment toxicity in 10%, other AIDS-related illnesses in 25% and other causes in 4%. Survival was shorter for patients with bone marrow involvement and for those with poor performance status. HIV-associated GI lymphoma has a poor prognosis despite good initial response to chemotherapy and is associated with a higher perforation rate than in HIV negative patients.
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PMID:HIV-associated lymphoma of the gastrointestinal tract: the University of Toronto AIDS-Lymphoma Study Group experience. 771 41

We conducted a retrospective cohort study to evaluate the occurrence of bacteremia and associated mortality among hospitalized patients who were seropositive for the human immunodeficiency virus (HIV) and who developed fever and neutropenia following antineoplastic chemotherapy or for other reasons. Review of medical records revealed 224 episodes in 142 patients. Of these episodes, 57% occurred following antineoplastic chemotherapy, and 43% occurred under other circumstances. Members of the chemotherapy group had significantly less-advanced HIV disease, a lower mean absolute-neutrophil-count nadir, and a shorter duration of hospitalization. There was no difference between the two groups in the frequency of bacteremia or mortality due to all causes when they were compared by multivariate analysis. Statistically significant univariate and multivariate predictors of bacteremia included sepsis syndrome and concurrent infection. Predictors of mortality included sepsis syndrome, concurrent infection, bacteremia, and antimicrobial therapy. This study suggests that the cause of neutropenia in HIV-seropositive patients is not a predictor of the outcome of fever and neutropenic episodes. Instead, clinical presentation and concomitant illnesses have a greater impact on outcome for a patient.
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PMID:Outcome for hospitalized patients with fever and neutropenia who are infected with the human immunodeficiency virus. 774 43

From a cohort of 837 adult, mainly homosexual HIV-infected patients, 76 bacteremic/fungemic episodes were identified in 63 patients over a 5-year period. Compared with an age-matched reference population with an incidence of 10.3 bacteremias/10,000 person-years, the incidence was 170 among pre-AIDS (p < 0.001) and 3,200 among AIDS patients (p < 0.001). Staphylococcal infections comprised 35% of all episodes, while the HIV-related pathogens Streptococcus pneumoniae, Salmonella spp. and C. neoformans together accounted for 34%. The overall mortality associated with clinical bacteremia was 12%, but nil for Salmonella spp. and S. pneumoniae. Predisposing factors for the infection were: low CD4 count (< 100 x 10(6)/l) in 71%, permanent intravenous line, 44%; neutropenia, 11% and active intravenous drug abuse, 7%. Hence, in this population, intensified hygienic precautions for intravenous lines should be the primary target for intervention. Long-term cotrimoxazole prophylaxis may prevent bacteremia with S. pneumoniae and Salmonella spp.
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PMID:Bacteremia in HIV-positive and AIDS patients: incidence, species distribution, risk-factors, outcome, and influence of long-term prophylactic antibiotic treatment. 774 85

One hundred immunocompromised HIV negative patients with microbiologically positive pneumonia underwent bronchoalveolar lavage (BAL) studies. Thirty cases showed peripheral neutropenia (< 1000 neutrophils/microL), 70 did not. The total cell number in BAL, the differential cell counts, and the lymphocyte subsets (CD4, CD8, CD19, CD57) were measured. Patients with pneumonia and normal or elevated peripheral neutrophils had a significantly increased total number of cells in BAL compared to patients with peripheral neutropenia (3.2 +/- 2 vs 1.3 +/- 0.6 x 10(5) cells/ml2 lavage fluid, p < 0.01). Ninety percent of the BAL differential cell counts obtained in patients exceeding 1000 neutrophils/microL showed a lymphocytic and/or neutrophilic alveolitis, whereas only 54% of patients with peripheral neutropenia displayed abnormal counts (p < 0.01). Yet the typical pattern of neutrophilic alveolitis was found more often for peripheral neutrophil counts over 1000/microL with high significance (p < 0.0001). Abnormal BAL cell patterns for neutropenic patients uniformly showed a lymphocytic alveolitis, only 10% additionally conformed with the pattern of neutrophilic alveolitis. Patients with pneumonia with and without peripheral neutropenia had similar findings in BAL lymphocyte subsets and exhibited a reduced CD4/CD8 ratio compared to controls (p < 0.05). The high susceptibility of severe neutropenic patients to pulmonary, especially fungal infections may be explained by the local lack of neutrophils.
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PMID:Differential cell count and lymphocyte subsets in bronchoalveolar lavage during pneumonia with and without peripheral neutropenia. 777 4

Retinoids have anti-tumor activity in several malignant and premalignant conditions. Since Kaposi's sarcoma is regulated by steroid hormones both in vivo and in vitro, we hypothesized that retinoids may have anti-tumor effects in AIDS-related Kaposi's sarcoma. Thus, 27 patients with mucocutaneous, non-visceral AIDS-related Kaposi's sarcoma were treated with all-trans retinoic acid (tRA). Poor tolerance was observed at the initial starting dose of 150 mg/m2, and thus subsequent patients were treated using a weekly dose escalation, starting with 45 mg/m2 (given daily, in subdivided doses), to the target dose of 150 mg/m2 (given daily in three subdivided doses). Nearly half (46%) of the patients had extensive mucocutaneous disease with over 25 lesions. No patient had received prior cytotoxic chemotherapy. Ten patients had CD4 lymphocytes of 200/mm3 or greater (strata I); and 17 had under 200/mm3 CD4 lymphocytes (strata II). The median of the average daily tRA dose administered was 150 mg (90 mg/m2; there was no significant difference in the dose tolerance between the two strata). Adverse effects consisted of transient mild to moderate headaches in 65% of patients, mild to moderate skin dryness and cheilitis in 61%, and nausea and vomiting in 31%. Hematologic toxicities included hypertriglyceridemia in 62%, anemia in 23%, and neutropenia in 23%. Partial response to therapy was observed in 4/24 (17%) evaluable patients, occurring after 12, 20, 24, and 28 weeks of therapy, and lasting 4-24 weeks. Three responders had baseline CD4 lymphocyte counts < 200/mm3. Three additional patients experienced reduction in measured indicator lesions of greater than 25% but less than 50%, and seven patients experienced disease stabilization of 16 weeks or greater. In evaluable patients, the median time to disease progression was 22 weeks and the overall median survival in all patients was 27.3 months. No significant changes in CD4 lymphocyte counts, p24 antigen, and beta 2 microglobulin were observed over time. However, a statistically significant increase was observed in soluble IL-2 receptor levels while on tRA (p = 0.037). We conclude that tRA has activity in patients with mucocutaneous AIDS-related Kaposi's sarcoma with acceptable toxicity. tRA has immunological effects without upregulation of HIV parameters. Additional studies in combinations or with more active retinoids are warranted.
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PMID:All-trans retinoic acid for the treatment of AIDS-related Kaposi's sarcoma: results of a pilot phase II study. 780 21


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