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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Zidovudine (AZT) is a potent inhibitor of the replication of the human immunodeficiency virus (HIV), and it has been shown to improve survival in advanced HIV disease. We conducted a randomized, double-blind trial in adults with asymptomatic HIV infection who had CD4+ cell counts of fewer than 500 per cubic millimeter on entry into the study. The subjects (92 percent male) were randomly assigned to one of three treatment groups: placebo (428 subjects); zidovudine, 500 mg per day (453); or zidovudine, 1500 mg per day (457). After a mean follow-up of 55 weeks (range, 19 to 107), 33 of the subjects assigned to placebo had the acquired immunodeficiency syndrome (AIDS), as compared with 11 of those assigned to receive 500 mg of zidovudine (P = 0.002; relative risk, 2.8; 95 percent confidence interval, 1.4 to 5.6) and 14 of those assigned to receive 1500 mg of zidovudine (P = 0.05; relative risk, 1.9; 95 percent confidence interval, 1.0 to 3.5). In the three treatment groups, the rates of progression (per 100 person-years) to either AIDS or advanced AIDS-related complex were 7.6, 3.6, and 4.3, respectively. As compared with those assigned to placebo, the subjects in the zidovudine groups had significant increases in the number of CD4+ cells and significant declines in p24 antigen levels. In the 1500-mg zidovudine group, severe hematologic toxicity (anemia or neutropenia) was more frequent than in the other groups (P less than 0.0001). In the 500-mg zidovudine group, nausea was the only toxicity that was significantly more frequent (in 3.3 percent) than in the placebo group (P = 0.001). We conclude that zidovudine is safe and effective in persons with asymptomatic HIV infection and fewer than 500 CD4+ cells per cubic millimeter. Additional study will be required to determine whether such treatment will ultimately improve survival for persons infected with HIV.
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PMID:Zidovudine in asymptomatic human immunodeficiency virus infection. A controlled trial in persons with fewer than 500 CD4-positive cells per cubic millimeter. The AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases. 238 74

To investigate whether there are variations in the growth capacity of HIV in peripheral blood mononuclear cell (PMBC) preparations from different individuals, PBMC cultures prepared from 27 healthy donors were infected with the fresh HIV-1 isolates JH/3 or JMH/1. After infection of the PBMC with HIV, the culture fluid was checked for infectivity (TCID50) and the level of p24 antigen. Significant diversity was observed in these values in different individuals. No correlation between the percentage of CD4-positive lymphocytes or the growth ability of PBMC and TCID50 was shown. Whether PBMC was infected with JH/3 or JMH/1 also made no difference. In some cases, however, the culture fluid possessed high (or low) p24 levels despite a low (or high) infectious virus yield. The E-rosette-positive cell fraction was separated from the PBMC preparations which showed the highest and the lowest virus yield, and the yield was determined after infection with JMH/1. The difference in virus yield and the TCID50/p24 ratio between these donors was also observed in these T-cell-enriched cell cultures. The results suggest that variations in the growth capacity of HIV in different PBMC preparations are due to the T-cell population and that the source of the PBMC influences not only the binding of the virions onto the cell surface but also the replication of the virus in the cell.
AIDS 1990 Jan
PMID:Variations in growth capacity of HIV in peripheral blood mononuclear cell preparations from different individuals. 196 80

The diagnostic value of the CD4 cell counts and the HIV p24 antigen were evaluated in a consecutive series of 105 HIV-infected patients experiencing 128 episodes of pulmonary symptoms which required bronchoscopy. One-third of patients with opportunistic infection (OI) had CD4 counts greater than 0.200 x 10(9)/l, and 60% of patients without OI had CD4 counts less than 0.200 x 10(9)/l; 47 and 42% of patients with and without OI, respectively, had detectable p24 antigen in serum. Only 36% of the patients with OI presented the combination of CD4 cells less than 0.200 x 10(9)/l and p24 in serum. In conclusion, the CD4 cell counts and the presence of p24 antigen in serum had a very limited predictive value for the presence of OI in HIV-infected patients with pulmonary symptoms.
AIDS 1990 Feb
PMID:CD4 lymphocyte counts and serum p24 antigen of no diagnostic value in monitoring HIV-infected patients with pulmonary symptoms. 197 Feb 56

A flow cytometric assay has been developed to detect and quantitate human immunodeficiency virus (HIV)-infected peripheral blood mononuclear cells obtained from HIV-seropositive patients. Peripheral blood was obtained from patients attending an acquired immune deficiency syndrome clinic, and mononuclear cells were separated by centrifugation onto Ficoll-Hypaque. The cell layer at the interface was removed, washed in phosphate-buffered saline without Ca2+ and Mg2+, and fixed with 90% methanol, and intracellular HIV antigens were detected by indirect immunofluorescence with monoclonal antibodies to HIV antigens as the primary antibody and fluorescein isothiocyanate-conjugated goat anti-mouse immunoglobulin G F(ab')2 antibody as the secondary antibody. DNA content was determined by propidium diiodide staining after RNase treatment. These fluorochrome-treated cells were analyzed for two-color fluorescence by flow cytometry. The results showed that HIV-infected cells in peripheral blood that have been treated with monoclonal antibodies to the p24 or nef antigens of HIV can be detected and quantitated by flow cytometry. The percentage of p24 antigen-positive mononuclear cells had a significant correlation (P = 0.0001) with the clinical status of the patient, i.e., those with a high percentage of p24 antigen-positive cells had a poorer prognosis than those with a lower percentage of p24 antigen-positive mononuclear cells. In addition, for those in Centers for Disease Control groups III and IV, there was an inverse correlation between the percentage of p24 antigen-positive mononuclear cells and the number of T4 cells. However, cell-associated antigen detection by flow cytometry did not correlate with detection of antigen in sera of HIV-seropositive patients by the standard antigen capture enzyme-linked immunosorbent assay. This lack of correlation was probably due to the presence of immune complexes in the sera of HIV-seropositive patients. These results suggest that flow cytometry can be used as a rapid, sensitive, and quantitative assay system for the determination of the antigen status of HIV-seropositive patients and that it may be more useful as an indicator of disease progression than the currently used antigen detection methods.
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PMID:Detection and quantitation of human immunodeficiency virus-infected peripheral blood mononuclear cells by flow cytometry. 197 May 76

To define the impact of human immunodeficiency virus (HIV) infection in Africa, clinical and laboratory investigations were conducted on 265 HIV-seropositive outpatients in Zimbabwe. Twenty-four of the study subjects were asymptomatic (ASX), 124 had persistent generalized lymphadenopathy (PGL), and 117 had AIDS-related complex (ARC). HIV infection was assessed by commercial ELISA, Western blots, synthetic peptide ELISA, and measurement of p24 antigen. Serum immunoglobulins, lymphocyte mitogen responses, and CD4+ cell numbers were obtained in 54 sequential patients. Compared to seronegative subjects, mean CD4+ cell numbers were decreased and serum immunoglobulins, particularly IgM and IgG, were increased in all groups of seropositive subjects. Lymphocyte proliferative responses to phytohemagglutinin and concanavalin A decreased progressively in ASX, PGL, and ARC patients and were significantly lower in PGL and ARC patients compared to seronegative controls. Generalized lymphadenopathy was present in 234/265 (88%) of patients. Lymph node biopsies in 100 patients demonstrated follicular hyperplasia in 97 and Mycobacterium tuberculosis in 3. Of 165 patients followed for a median of 6 months, 5 developed the acquired immune deficiency syndrome (AIDS). Symptoms of ARC, low CD4+ cell number, and p24 antigen were predictive of the development of AIDS in Zimbabwe.
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PMID:Clinical and laboratory characteristics of HIV-1 infection in Zimbabwe. 197 89

Eighteen asymptomatic men with persistent human immunodeficiency virus type 1 (HIV-1) p24 antigenemia were treated with zidovudine 250-500 mg (+/- acyclovir 800 mg) 6-hourly for 4-12 weeks, and thereafter with zidovudine 500 mg (+/- acyclovir 1600 mg) 12-hourly for 92 weeks. Six additional HIV-1 p24 antigenemic subjects were treated with zidovudine 500 mg 12-hourly for 76 weeks. Disease progression occurred in 4 subjects, despite sustained reduction of serum HIV-1 p24 antigen levels: Pneumocystis carinii pneumonia was diagnosed after 60, 80, 90 and 93 weeks, respectively. The median CD4+ cell count of these 4 men at study entry was 0.2 x 10(9)/l, and it declined to 0.07 x 10(9)/l at the moment AIDS was diagnosed. In 20 subjects no disease progression occurred. The median CD4+ cell count of these 20 men at study entry was 0.4 x 10(9)/l and it was 0.45 x 10(9)/l at the end of the study period. Median serum HIV-1 p24 antigen levels at the end of the study period were 42% lower than at study entry in these 20 subjects. In 5/20 men, an initial decline was followed by a rise in antigen levels to above pretreatment value. Treatment with zidovudine was well tolerated. Anemia caused symptoms in 3/24 men, but prolonged leucopenia or neutropenia did not occur. None developed clinical or convincing biochemical evidence of zidovudine-associated myopathy.
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PMID:Long-term zidovudine treatment of asymptomatic HIV-1-infected subjects. 197 21

This study was undertaken to define the risk of AIDS in a cohort of 250 HIV-seropositive patients identified by their clinical and biological status. All patients were enrolled between October 1985 and March 1988. They were classified according to clinical classes A, asymptomatic (n = 97); B, lymphadenopathic (n = 123); and C, AIDS-related complex, (n = 30). Also as CD4 cell stages 1 (CD4 greater than or equal to 600/microliters; n = 126); 2 (CD4 less than 600 and greater than or equal to 300/microliters; n = 83); and 3 (CD4 less than 300/microliters; n = 41); and serum p24 antigen positive (n = 48) or negative (n = 202). All patients were evaluated every 3-6 months, until AIDS development or April 1989: 29 cases of AIDS occurred during the follow-up period. The risk of AIDS in class C is very high (64% at 2 years) compared with the 3-year risk of classes A (13%) and B (25%). On the other hand the three CD4 stages have significantly different prognosis (stage 1 6%; stage 2 22%; and stage 3 89%; P less than 10(-2]. Antigen p24 negative and positive patients have also different prognosis (18% and 53%; P less than 10(-4]. Interestingly, p24 antigen conserved its prognostic value in stage 2 (positive 37%, negative 16%) while stages 1 are at low risk of AIDS and stages 3 at high risk whatever their p24 antigen status. We have also identified the risk of becoming stage 3 and/or p24 antigen positive in p24 antigen negative patients at stages 1 and 2 (respectively, 18% and 47%). This classification should serve to design randomized trials better with experimental drugs with earlier end-points than AIDS onset.
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PMID:Actuarial rate of clinical and biological progression in a cohort of 250 HIV-1-seropositive subjects. Laennec HIV Study Group. 197 69

2',3'-Dideoxyinosine (didanosine; ddI) was administered to 37 adults with AIDS or AIDS-related complex in an escalating-dose phase I study. Groups of three or four patients received intravenous dosages of 0.4 mg/(kg.d) to 25.6 mg/(kg.d) divided into two or three daily doses for 2 weeks, followed by oral ddI at twice the intravenous dosages. When given with antacids, ddI was well absorbed by the oral route and penetrated into the cerebrospinal fluid. The patients had an increase in mean number of CD4+ cells from 114/mm3 at entry to 161/mm3 at week 6 (P = .00004). They also had an increase in the CD4+/CD8+ ratio and in total number of lymphocytes. Sixteen of 18 evaluable patients had a decrease in levels of human immunodeficiency virus p24 antigen by week 6 (P = .0034). Many patients reported increased energy and appetite and gained weight. Dose-limiting toxicities at high dosages were painful peripheral neuropathy and sporadic pancreatitis. However, dosages up to 9.6 mg/(kg.d) have been tolerated in patients for 11-14 months. Thus, ddI has activity against human immunodeficiency virus at dosages that can be tolerated for approximately 1 year. However, life-threatening pancreatitis is a possible complication even at low dosages, and the best ways to manage and avoid adverse effects are still under study.
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PMID:The National Cancer Institute phase I study of 2',3'-dideoxyinosine administration in adults with AIDS or AIDS-related complex: analysis of activity and toxicity profiles. 197 24

We performed a phase I study of escalating dosages of 2',3'-dideoxyinosine (didanosine; ddI) in 19 patients with AIDS or AIDS-related complex in order (1) to establish the maximal tolerated dosage, (2) to determine the nature of toxic adverse effects, (3) to measure changes in levels of circulating human immunodeficiency virus p24 antigen and in CD4+ cell counts, and (4) to evaluate the pharmacokinetics of ddI. Almost all patients had received zidovudine therapy previously. The maximal tolerated dosage of ddI was found to be approximately 12 mg/(kg.d) when it was administered orally for 28 weeks. The major dosage-limiting adverse effects encountered were neuropathy, pancreatitis, and hepatitis. These occurred at dosages higher than those associated with decreases in levels of p24 antigen. The major toxic effects of ddI are different from those associated with zidovudine. At the proper dosage, ddI may prove to be an effective agent for the chronic treatment of infection with human immunodeficiency virus and should be especially useful in the treatment of patients who cannot tolerate zidovudine.
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PMID:Phase I study of 2',3'-dideoxyinosine: experience with 19 patients at New York University Medical Center. 197 25

Twenty-one patients with AIDS or AIDS-related complex (ARC) received 2',3'-dideoxyinosine (didanosine; ddI) intravenously and then orally (initial dosages of 0.4 mg/kg and 0.8 mg/kg every 12 hours, respectively) for 6-44 weeks in an escalating-dose study. The major dose-limiting effects were peripheral neuropathy (three patients) and pancreatitis (two patients), which were observed at dosages greater than or equal to 20 mg/(kg.d). Hyperuricemia occurred at greater than or equal to 30 mg/(kg.d). No hematologic toxicity developed except for possible sporadic thrombocytopenia (two patients). Significant decreases in serum levels of p24 antigen and increases in CD4+ and CD8+ lymphocytes were noted at 2, 6, and 10-20 weeks and over a wide range of dosages, including the lowest given. Most patients had an increased feeling of well-being and/or a weight gain of greater than or equal to 2 kg at 6 weeks. For this population, ddI has promise as a therapeutic agent, thus warranting further study of this agent in controlled clinical trials.
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PMID:2',3'-Dideoxyinosine in patients with AIDS or AIDS-related complex. 197 26


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