Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We compared the occurrences of several types of infections in HIV-infected patients participating in a randomized clinical trial of three treatment strategies given for the primary prevention of Pneumocystis carinii pneumonia (PCP) and toxoplasmosis. In a phase III open label trial, 842 patients with HIV infection and fewer than 200 CD4+ cells/mm(3) received zidovudine (standard dose) plus one of three randomly assigned prophylactic agents: trimethoprim-sulfamethoxazole (TMP-SMZ), or dapsone (DAP), or aerosolized pentamidine (AP). Patients developing intolerance to treatment were crossed over to another predefined prophylactic therapy. Patients were monitored for infections every other week for 8 weeks and then monthly until the study was completed. Primary statistical models were proportional hazards models adapted to recurrent end points. In an intent-to-treat analysis, compared with AP and DAP, TMP-SMZ significantly reduced the risk of any bacterial infection (combining all distinct types) (p = 0.02 and p = 0.01, respectively). When considering distinct types separately, compared with AP, TMP-SMZ significantly reduced the risk of infectious diarrhea (p = 0.04); compared with DAP, AP and TMP-SMZ significantly reduced the risk of sinusitis/otitis media (p = 0.03 and p = 0.04, respectively); compared with AP and DAP, TMP-SMZ significantly reduced the risk of a second occurrence of pneumonia (p = 0.04 and 0.02, respectively). For any bacterial infection, infection rates per 100 patient-years of follow-up were 31, 39, and 38 for TMP-SMZ, DAP, and AP, respectively. In patients with advanced HIV infection not taking highly active antiretroviral therapy, the treatment strategy that initiates prophylaxis with TMP-SMZ is superior to those initiating with AP or DAP for preventing any bacterial infection, with most of the advantage manifested through infectious diarrhea, sinusitis/otitis media, and pneumonia.
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PMID:Efficacy of trimethoprim-sulfamethoxazole for the prevention of bacterial infections in a randomized prophylaxis trial of patients with advanced HIV infection. 1183 41

The thymidine (dThd) kinase (TK) encoded by herpes simplex virus type 1 (HSV-1) is not only endowed with dThd kinase, but also with thymidylate (dTMP) kinase and 2'-deoxycytidine (dCyd) kinase (dCK) activity. HSV-1 TK also recognizes a variety of antiherpetic guanine nucleoside analogues such as acyclovir (ACV), ganciclovir (GCV), lobucavir (LBV), penciclovir (PCV), and others (i.e., A5021). Site-directed mutagenesis of the highly conserved Ala-167 to Tyr in HSV-1 TK completely abolished TK, dTMP-K, and dCK activity, but maintained ACV-, GCV-, LBV-, PCV-, and A5021-phosphorylating capacity. A variety of 5-substituted pyrimidine nucleoside substrates, but also a number of selective HSV-1 TK inhibitors structurally related to thymine lost significant binding affinity for the mutant enzyme and did not markedly compete with GCV phosphorylation by the mutant enzyme. These findings could be explained by computer-assisted modeling data that revealed steric hindrance of the pyrimidine ring in the HSV-1 TK active site by the large 4-hydroxybenzyl ring of 167-Tyr, while the positioning of the purine ring of guanine-based HIV-1 TK substrates in the active site was kept virtually unaltered. Surprisingly, the efficiency of conversion the antiherpetic 2'-deoxyguanosine analogues ACV, GCV, LBV, PCV, and A5021 to their phosphorylated forms by the A167Y mutant HSV-1 TK was far more pronounced than for the wild-type enzyme. Therefore, the single A167Y mutation converts the wild-type HSV-1 TK from a predominantly pyrimidine nucleos(t)ide kinase into a virtually exclusive purine (guanine) nucleoside analogue kinase.
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PMID:The A167Y mutation converts the herpes simplex virus type 1 thymidine kinase into a guanosine analogue kinase. 1200 16

The case of a patient with a newly diagnosed HIV infection and Pneumocystis carinii pneumonia is presented. Despite treatment with high-dose trimethoprim/sulfamethoxazole (TMP/SMX) and prednisone with initial improvement, the patient acutely deteriorated with severe acidosis and died on the 4th day of hospitalization. Cryptococcus neoformans grew the next day in broncheoalveolar lavage (BAL) and blood culture. As simultaneous presence of more than one opportunistic infection can occur in these patients, systematic workup for other common opportunistic infections must be performed.
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PMID:Fatal sepsis in an AIDS patient during therapy for Pneumocystis carinii pneumonia. 1238 94

African human immunodeficiency virus type 1 (HIV-1)-infected children were evaluated to define the burden of Pneumocystis carinii pneumonia (PCP) and its interaction with bacterial and viral pathogens. P. carinii was identified in 101 (43.7%) of 231 episodes of pneumonia among 185 HIV-1-infected children (median age, 4.5 months; range, 1.7-27.3 months). Receipt of trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis was not associated with a significant reduction (36%; 95% confidence interval [CI], -15.4% to 64.5%) in isolation of P. carinii among children considered to have received adequate prophylaxis (37.7% of children) compared with children who had never received any prophylaxis (48.5% of children). However, deaths among children with PCP who had been taking TMP-SMX prophylaxis were markedly reduced (98.6%; 95% CI, 89.1%-99.8%) compared with children who were not taking prophylaxis. Concurrent P. carinii infection was observed in 6 of 18, 11 of 26, and 4 of 6 HIV-1-infected children who had bacteremia, a respiratory virus isolated, or Mycobacterium species isolated, respectively.
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PMID:Ineffectiveness of trimethoprim-sulfamethoxazole prophylaxis and the importance of bacterial and viral coinfections in African children with Pneumocystis carinii pneumonia. 1295 58

A simulation model of human immunodeficiency virus (HIV) disease, which incorporated French data on the progression of HIV disease in the absence of antiretroviral therapy and on cost, was used to determine the clinical impact and cost-effectiveness of different strategies for the prevention of opportunistic infections in French patients who receive highly active antiretroviral therapy (HAART). Compared with use of no prophylaxis, use of trimethoprim-sulfamethoxazole (TMP-SMZ) increased per-person lifetime costs from euro 185,600 to euro 187,900 and quality-adjusted life expectancy from 112.2 to 113.7 months, for an incremental cost-effectiveness ratio of euro 18,700 per quality-adjusted life-year (euro/QALY) gained. Compared with use of TMP-SMZ alone, use of TMP-SMZ plus azithromycin cost euro 23,900/QALY gained; adding fluconazole cost an additional euro 54,500/QALY gained. All strategies that included oral ganciclovir had cost-effectiveness ratios that exceeded euro 100,000/QALY gained. In the era of HAART, on the basis of French data, prophylaxis against Pneumocystis carinii pneumonia, toxoplasmic encephalitis, and Mycobacterium avium complex bacteremia is cost-effective. Prophylaxis against fungal and cytomegalovirus infections is less cost-effective than are other therapeutic options for HIV disease and should remain of lower priority.
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PMID:Prevention of human immunodeficiency virus-related opportunistic infections in France: a cost-effectiveness analysis. 1249 Dec 7

The aim of this study was to compare the type and antimicrobial resistance patterns of bacteria cultured from blood or respiratory tract secretions by HIV status and the use of trimethoprim-sulphamethoxazole (TMP-SMX) prophylaxis in children hospitalized with community-acquired pneumonia. During a 1-year prospective study in Cape Town, South Africa, 250 children [median aged 6 (3-16) months] hospitalized with pneumonia were enrolled; 151 (60.4 per cent) were HIV-infected. The incidence of bacteremia [35 of 244 cultures (14.3 per cent)] did not differ by HIV status. Bacteria were cultured in 17 of 32 (53 per cent) bronchoalveolar lavage specimens (BAL), 128 of 210 (61 per cent) induced sputa and 166 of 231 (71 per cent) nasopharyngeal specimens (NPAs). The type and number of bacteria in respiratory secretions did not differ by HIV status, except for a higher rate of Staphylococcus aureus in sputum or BAL [22 of 146 (15 per cent) vs. 3 of 96 (3 per cent), p = 0.003] and NPAs [41 of 135 (30 per cent) vs. 9 of 96 (9 per cent), p < 0.001] of HIV-positive children. The use of TMP-SMX prophylaxis in HIV-infected children was associated with an increased nasopharyngeal carriage of S. aureus [22 of 51 (43 per cent) vs. 17 of 79 (22 per cent), p = 0.009]. The rising prevalence of HIV infection and the use of TMP-SMX prophylaxis may alter the spectrum of colonizing and pathogenic bacteria in children in developing countries.
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PMID:The impact of HIV infection and trimethoprim-sulphamethoxazole prophylaxis on bacterial isolates from children with community-acquired pneumonia in South Africa. 1272 88

Pneumococcal pneumonia and meningitis are common infectious disease problems in people who are HIV seropositive in southern Africa. For many years two inexpensive antibiotics, penicillin and trimethoprim-sulphamethoxazole (TMP-SMX) had been effective in treatment, but recently resistance to these agents has been reported from many parts of the world. This study was designed to determine the antimicrobial resistance patterns in invasive pneumococci from hospital patients in Harare, Zimbabwe. A total of 160 isolates of Streptococcus pneumoniae from blood cultures and CSF cultures were examined. The isolates came from adults and children in hospital in Harare between 1994 and 2000. The majority of isolates came from HIV positive adults (74%) and children (75%). Isolates of pneumococci with an MIC of 1.0 mg/l or more were first seen in 1997 and by 2000 they made up 35% of all isolates. Significantly more isolates from HIV seropositive patients (50%) showed reduced susceptibility to penicillin compared with isolates from HIV seronegative patients (16%), and high level resistance (MIC 1.0 mg/l or higher) was found in 16% isolates from HIV positive patients compared with 6% isolates from HIV seronegative patients. Resistance to TMP-SMX was common, with more than 50% isolates from HIV positive and HIV negative patients having reduced susceptibility to this antibiotic combination.
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PMID:Rapid emergence of resistance to penicillin and trimethoprim-sulphamethoxazole in invasive Streptococcus pneumoniae in Zimbabwe. 1279 69

Trimethoprim-sulfamethoxazole (TMP-SMZ) is one of the most commonly used antibiotics. Although many of its adverse effects are well recognized, TMP-SMZ related hepatotoxicity is considered rare and is usually characterized by cholestasis or mixed hepatocellular-holestatic reactions. In this study, we describe the case of a previously healthy young man with acute fulminant liver failure caused by TMP-SMZ. The patient presented with complaints of 'flu-like' symptoms with myalgia and fever after taking TMP-SMZ for 7 d for otitis externa. The patient subsequently developed fever, worsening jaundice, and a rash on his neck and chest. Liver enzymes peaked on day 3 with alanine aminotransferase (ALT) 11,549, aspartate aminotransferase (AST) 23,289, alkaline phosphatase 245, and total bilirubin 10.3 mg/dL, with a conjugated bilirubin of 8.3 mg/dL, prothrombin time (PT) 60.5 s, partial normalized ratio (PTT) 49 s, and international normalized ratio (INR) 7.5. Of note, acetaminophen level on admission was undetectable. Serology for hepatitis A, B, C, cytomegalovirus, HIV, toxoplasmosis, and blood cultures were all negative. The patient developed hepatic encephalopathy with hallucination on day 4. Laboratory tests revealed a serum ammonia level of 190 U, serum creatinine kinase (CK) 10,466 (42 on admission), serum creatinine 8.2 mg/dL (1.2 on admission), and significant metabolic acidosis. Renal ultrasound was unremarkable. The patient was started on hemodialysis for acute renal failure. Meanwhile, liver transplantation assessment was also initiated. On day 8 post-admission (15 d after taking TMP-SMZ), the patient received a successful orthotopic liver transplant.
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PMID:Successful orthotopic liver transplantation after trimethoprim-sulfamethoxazole associated fulminant liver failure. 1470 31

Rhodococcus equi is a facultative intracellular, obligate aerobe, partially acid fast, gram-positive pathogen that causes cavitary pneumonia in animals and immunocompromised humans. We describe 8 cases of R. equi pneumonia in patients with advanced HIV infection (CD4 counts less than 100/mm3), 7 males and 1 female (mean age 30.8 years), observed between 1991 and 1994. A history of exposure to farm animals was found in 4 patients. The most common presenting symptoms were fever, malaise, dyspnea, cough and hemoptysis, chest pain and weight loss. Chest x-rays showed tipical focal area of consolidation throughout the lung (3 upper, 3 lower and 2 middle fields) associated with cavitation in 4 cases. The definitive diagnosis in our hands was delayed only in the first case in which conflicting data resulted from blood culture (Bacillus sp. isolation) and sputum examen (acid-fast bacterium in the Ziehl-Neelsen stain). Final microbiological diagnosis depended on blood cultures (n=5), bronchoalveolar lavage (n=1), sputum (n=1), lung biopsy (n=1). All the patients were treated with prolonged courses of antibiotic therapy (259 days, range 120-340 in 6 dead patients; more than one year and two months respectively in two patients alive). According to microbial susceptibility TMP/SMX, vancomycin, imipenem, rifampin, aminoglycosides, macrolides and quinolons were more frequently used. Resistant R. equi mutants were selected during therapy with TMP/SMX (n=2), rifampin (n=1) and erythromycin (n=1). Five patient underwent pulmonary lobectomy after exclusion of metastatic bacterial lesions. Only 2 patients are alive, one after 365 days of antibiotic therapy and upper lung lobectomy, one after 60 days of antibiotic therapy. Optimal antimicrobial therapy and the role of surgery remain, in our experience, uncertain.
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PMID:[Not Available]. 1503 8

We studied all human immunodeficiency virus (HIV)-infected patients with invasive pneumococcal disease who received their diagnosis during 1996-2002 to investigate the incidence of this disease in the highly active antiretroviral therapy era and to study the influence of CD4 lymphocyte count on the clinical presentation and outcome of disease. The overall incidence of invasive pneumococcal disease was 11.3 cases per 100,000 person-years in adult patients without known HIV infection and 677 cases per 100,000 person-years in HIV-infected patients. This incidence remained stable over the study period. Clinical presentation, severity of illness, and number of recurrent episodes were similar in patients with CD4+ cell counts of >200 or < or =200 cells/ microL. Patients receiving trimethoprim-sulfamethoxazole (TMP-SMZ) were more likely to present with TMP-SMZ-resistant pneumococci than were those who were not receiving this agent (76.7% vs. 43.6%; P=.007). The mortality rate was high (21%).
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PMID:Invasive pneumococcal disease in patients infected with HIV: still a threat in the era of highly active antiretroviral therapy. 1515 52


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