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

In 1989, the United States Public Health Service convened a Task Force of experts to consider the expanding knowledge base about prevention of Pneumocystis carinii pneumonia (PCP) among adults and adolescents (greater than or equal to 13 years of age) with human immunodeficiency virus (HIV) infection. This Task Force concluded that the morbidity, mortality, and cost due to PCP could be substantially reduced by appropriate use of antipneumocystis prophylaxis in subgroups of HIV-infected patients known to be at high risk, and developed recommendations for the administration of prophylactic regimens (1). The recommendations state that CD4+ T-lymphocyte counts should be monitored prospectively at 3- to 6-month intervals and prophylaxis should be instituted when patients become immunologically susceptible to PCP. Susceptibility was defined by a CD4+ T-lymphocyte count less than 200 cells/microliters or less than 20% of total circulating lymphocytes, or the occurrence of a previous episode of PCP. The goal of this approach was to reduce the frequency both of initial episodes of PCP (primary prophylaxis) and of relapses or recurrences (secondary prophylaxis). Either oral trimethoprim-sulfamethoxazole (TMP-SMX) or aerosol pentamidine was recommended for prophylaxis, but because direct comparative data were lacking, neither regimen was endorsed as "preferred." Since the recommendations were issued in 1989, additional information has become available about the efficacy and safety of aerosol pentamidine and oral TMP-SMX. A trial sponsored by the National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group compared these two regimens in a prospective randomized study; in August 1991, this study was terminated by an independent data and safety monitoring board because statistically significantly fewer recurrences of PCP were observed in the oral TMP-SMX group than in the aerosol pentamidine group (2). On the basis of this finding and other studies assessing PCP prophylaxis, the Task Force was reconvened on October 5, 1991. This report contains the revised recommendations issued by the Task Force.
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PMID:Recommendations for prophylaxis against Pneumocystis carinii pneumonia for adults and adolescents infected with human immunodeficiency virus. 134 43

The inhibitory potency of 3'-azido-3'-deoxythymidine 5'-triphosphate (AZTTP) against HIV-1 reverse transcriptase (HIV-1 RT) has been further evaluated. The results indicate that the previously reported low Ki values for AZTTP against HIV-1 RT (2.35 nM) are due neither to the to the direct tight binding of AZTTP to HIV-1 RT nor to the interaction of the enzyme with AZTMP moiety terminated primer-templates, but instead they are an artifact of the use of a homotemplate-primer [poly(rA).oligo(dT)]. With a set of RNAs of defined sequence as templates, we demonstrate that the observed Ki value for AZTTP depends on the length of the poly(rA) region following the primer in the RNA template. The more adenosyl residues in the RNA template that are available for processive incorporation of TMP moieties, the lower is the observed Ki value for AZTTP. Since the potencies of new inhibitors of HIV-1 RT are usually compared with that for AZTTP, these results have important consequences for the process of discovery of new HIV inhibitors that are of potential use in AIDS therapy.
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PMID:The observed inhibitory potency of 3'-azido-3'-deoxythymidine 5'-triphosphate for HIV-1 reverse transcriptase depends on the length of the poly(rA) region of the template. 137 Oct 70

Chronic exposure of H9 cells to 25 microM zidovudine (H9-AZT cells) causes a 2- to 3-fold increase in thymidine kinase (TK) activity (Agarwal RP, Int J Purines Pyrimidine Res, in press). The present study compared thymidine (TdR) and AZT anabolism in H9 and H9-AZT cells. After a 3.5-hr incubation with 10 microM TdR or AZT, the total intracellular accumulations of AZT (48.7 microM in H9 cells and 32.8 microM in H9-AZT cells) were 46.4% of TdR accumulation. Other major differences between TdR and AZT anabolism were: (i) the majority of TdR (84-87%) was incorporated into DNA compared to less than 1% of AZT; and (ii) whereas distribution of TdR in the nucleotides was TTP greater than TMP greater than TDP, zidovudine distributed was AZT-MP much greater than AZT-TP much greater than AZT-DP. Because of the poor substrate activity of AZT-MP for thymidylate kinase (TMP-kinase), most of the AZT (95-98%) remained as AZT-MP. TMP-kinase activities with TMP as substrate were 47.6 +/- 20.3 and 91.4 +/- 28.8 pmol/mg protein/min in H9 and H9-AZT cells, respectively. 5'-Nucleotidase activities with TMP as substrate were 428.9 +/- 37.8 and 255.9 +/- 28.7 pmol/mg protein/min in H9 and H9-AZT cells, respectively. Activities of these enzymes with AZT-MP as a substrate were very low. Despite an increase in TK and TMP-kinase, and a decrease in 5'-nucleotidase activities, the total intracellular accumulations of TdR and AZT were reduced significantly (P less than 0.05) to 67.5% in H9-AZT cells. Thymidine transport (0.66 to 0.68 pmol/sec/10(6) cells) was similar in both the cell lines. The severe reductions of TdR salvage caused by chronic exposure of cells to AZT, if it occurs in AIDS patients on AZT chemotherapy, may explain some of the long-term clinical toxicities of the drug.
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PMID:Thymidine and zidovudine metabolism in chronically zidovudine-exposed cells in vitro. 186 45

Pneumocystis carinii pneumonia complicated the course of two patients with multiple myeloma. The diagnosis was established in both cases by bronchoalveolar lavage, which demonstrated the typical pneumocysts. Clinical and roentgenographic improvement in both patients was observed following a course of trimethoprim-sulfamethoxazole. One patient had lymphocyte subsets performed with a CD4/CD8 ratio of 0.8; both patients were HIV antibody-negative by ELISA. Both patients tolerated prophylactic TMP-SMX given concurrently with the subsequent chemotherapy for myeloma. We suggest that the immune defect seen in multiple myeloma may have placed these patients at risk for opportunistic infections such as P carinii pneumonia; however, as opposed to patients with AIDS, our patients tolerated therapy with TMP-SMZ quite well.
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PMID:Pneumocystis carinii pneumonia complicating multiple myeloma. 199 21

Adverse effects are common in patients with acquired immunodeficiency syndrome (AIDS) who receive trimethoprim-sulfamethoxazole (TMP-SMX). Two patients experienced a rare anaphylactoid syndrome. Within hours of receiving a double-strength TMP-SMX tablet, a 28-year-old human immunodeficiency virus (HIV)-positive man developed fever, hypotension, and bilateral pulmonary infiltrates. Broad-spectrum antimicrobial therapy was begun but discontinued 2 days later when signs and symptoms resolved and specimens for Pneumocystis carinii were negative. A 38-year-old man developed rash, fever, hypotension, hyperbilirubinemia, renal dysfunction, and bilateral pulmonary infiltrates after taking two doses of oral TMP-SMX. Several antimicrobial agents, including parenteral pentamidine, were administered despite lack of evidence for P. carinii or other infection. four case reports of similar reactions in patients with AIDS have been published. Notable differences exist between the syndrome described and anaphylaxis. The TMP-SMX anaphylactoid reactions in patients with AIDS mimic sepsis or opportunistic infection, thus making diagnosis difficult.
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PMID:Trimethoprim-sulfamethoxazole anaphylactoid reactions in patients with AIDS: case reports and literature review. 228 64

Thirty-four homosexual patients with AIDS were treated for Pneumocystis carinii pneumonia between April 1984 and November 1985. All 31 survivors were treated with oral trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis immediately upon completion of intravenous therapy, despite the prior occurrence of hypersensitivity reactions to intravenous TMP-SMX in 21 of these patients. Only four patients had subsequent reactions to oral TMP-SMX requiring the drug's discontinuation. None of the patients remaining on prophylaxis developed recurrent Pneumocystis pneumonia. Oral TMP-SMX appears effective at preventing recurrent Pneumocystis pneumonia in patients with AIDS. Hypersensitivity reactions during therapy with TMP-SMX may not be a contraindication to continuation of therapy and subsequent oral prophylaxis.
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PMID:Successful prophylaxis of Pneumocystis carinii pneumonia with trimethoprim-sulfamethoxazole in AIDS patients with previous allergic reactions. 252 71

A total of 100 consecutive patients with AIDS were evaluated for efficacy and safety of treatment and secondary prophylaxis directed against Pneumocystis carinii pneumonia (PCP). 89 episodes of PCP were recorded in 75 patients. 63 of the 75 patients (84%) with a first episode of PCP were discharged. Of 72 patients with a first episode of PCP who were initially treated with trimethoprim-sulfamethoxazole. 76% completed therapy successfully. Side effects were common, but generally mild and tolerated during continued treatment. 7/11 patients (64%) with a first episode of PCP who required mechanical ventilation were discharged. Long term prognosis for these patients was not worse than for patients who did not require mechanical ventilation. Relapse of PCP occurred in 3/50 patients (6%) during secondary prophylaxis, 160 mg trimethoprim and 800 mg sulfamethoxazole (TMP-SMZ) every 24 h, compared to 11/16 (69%) patients who were not receiving prophylaxis (p less than 0.00001). No patients discontinued prophylaxis because of side effects. It is concluded that for most patients with AIDS and PCP, treatment and secondary prophylaxis with TMP-SMZ is safe and effective.
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PMID:The outcome of Pneumocystis carinii pneumonia in Danish patients with AIDS. 258 39

In 33 consecutive AIDS patients with a first episode of Pneumocystis carinii pneumonia (PCP) we evaluated treatment, outcome, recurrence rate and pyrimethamine as chemoprophylaxis in a 1-year follow-up. Only 2 patients had a CD4 lymphocyte cell count greater than 0.2 X 10(9)/l. Trimethoprim-sulfamethoxazole (TMP-SMX) was initially given to 32 patients but in 20 of these patients severe adverse reactions caused us to discontinue treatment. Of these 20 patients 11 were started on i.v./i.m. pentamidine but in 6 adverse reactions forced us to withdraw pentamidine. Patients were retrospectively divided with regard to duration of therapy into 2 groups. We could not find any difference between patients in Group 1 treated for less than or equal to 14 days and patients in Group 2 treated for greater than 14 days when comparing outcome, number of recurrences and mean time until recurrence. In 16/21 patients given only TMP-SMX initially in a high dose (means = 16 mg trimethoprim/kg/day), dose reduction was performed to means = 10.5 mg trimethoprim/kg/day after a mean time of 6.9 days. The case-fatality rate for these patients was 10% (2/21) and the overall case-fatality rate was 15% (5/33). We chose pyrimethamine (50-175 mg/week) as secondary prophylaxis for PCP. At 1-year follow-up another 16 patients had died (21/32) and 9/27 (33%) discharged patients had had one recurrence each of PCP. All recurrences occurred among patients treated with only TMP-SMX for the acute episode of PCP. Of these 27 discharged patients 23 had been given pyrimethamine and 8 (36%) of these had experienced a recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pneumocystis carinii pneumonia in Stockholm, Sweden: treatment, outcome, one-year-follow-up and pyrimethamine prophylaxis. 258 40

Pneumocystis carinii pneumonia (PCP) is the commonest opportunistic infection in AIDS patients. The diagnosis should be strongly suspected in patients who are cyanosed and who present with interstitial pneumonia. The management of PCP in AIDS patients is very similar to that in other groups with the same infection. Trimethoprim-sulphamethoxazole (TMP/SMZ) combinations or pentamidine remain the therapies of choice. Side effects of TMP/SMZ are much greater in AIDS patients than in other immuno-suppressed patients and are similar in frequency to those of pentamidine. Occasionally, pentamidine produces life-threatening complications. Trimetrexate with folinic acid is likely to be as effective against pneumocystis as the two first-line drugs and trimethoprim/dapsone combinations can be given orally and are clearly effective in moderately severe infections. Prophylaxis following an attack of PCP undoubtedly reduces the risk of re-infection, but may not materially alter the overall prognosis. The best drug regimen remains controversial but fortnightly inhaled pentamidine has the advantage of patient acceptability and very low risk of side-effects.
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PMID:Pneumocystis carinii pneumonia and its treatment in patients with AIDS. 265 17

The continuing growth of the acquired immunodeficiency syndrome (AIDS) epidemic has caused a parallel increase in patients with Pneumocystis carinii pneumonia (PCP). PCP has a wide spectrum of severity, from mild disease to severe parenchymal lung damage. Outcome is determined by severity of lung injury, the underlying physical condition of the patient, and concomitant infections. Both trimethoprim-sulfamethoxazole (TMP-SMX) and pentamidine are effective therapeutic agents; however, both cause a high incidence of adverse reactions. TMP-SMX therapy can be made safer by careful monitoring and dose adjustment. Pentamidine toxicity, especially hypoglycemia, appears to be cumulative dose-dependent. Experimental therapies, including TMP-dapsone and aerosolized pentamidine, appear promising in mild to moderate disease, while trimetrexate may be more effective in severe disease. Corticosteroids are unproven in decreasing mortality. Prophylaxis of PCP is possible with TMP-SMX but the high rate of adverse reactions make long-term therapy difficult. Other oral therapies such as dapsone, pyrimethamine/sulfadoxine are also promising but not yet tested. Aerosolized pentamidine is effective and safe for prophylaxis regimen when administered correctly. Airway irritation as manifested by cough and/or wheezing is a common adverse effect of aerosolized pentamidine.
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PMID:Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome: pathophysiology, therapy, and prevention. 266 34


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