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)

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

HIV-1 reverse transcriptase can remove chain terminators from blocked DNA ends through a nucleotide-dependent mechanism. We show that the catalytic efficiency of the removal reaction can vary several hundred-fold in different sequence contexts and is most strongly affected by the nature of the base pair at the 3'-primer terminus and the six base pairs upstream of it. Similar effects of the upstream sequence were observed with primer-templates terminated with 2',3'-dideoxy-AMP, 2',3'-dideoxy-CMP, or 2',3'-dideoxy-GMP. However, the removal of 2',3'-dideoxy-TMP or 3'-azido-2',3'-dideoxy-TMP was much less influenced by upstream primer-template sequence, and the rate of excision of these thymidylate analogues was greater than or equal to that of the other chain-terminating residues in each sequence context tested. These results strongly indicate that the primer terminus and adjacent upstream base pairs interact with reverse transcriptase in a sequence-dependent manner that affects the removal reaction. We conclude that primer-template sequence context is a major factor to consider when evaluating the removal of different chain terminators by HIV-1 reverse transcriptase.
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PMID:Effects of primer-template sequence on ATP-dependent removal of chain-terminating nucleotide analogues by HIV-1 reverse transcriptase. 1530 46

Pneumocystis pneumonia (PCP) remains a major cause of illness and death in HIV-infected persons. Sulfa drugs, trimethoprim-sulfamethoxazole (TMP-SMX) and dapsone are mainstays of PCP treatment and prophylaxis. While prophylaxis has reduced the incidence of PCP, its use has raised concerns about development of resistant organisms. The inability to culture human Pneumocystis, Pneumocystis jirovecii, in a standardized culture system prevents routine susceptibility testing and detection of drug resistance. In other microorganisms, sulfa drug resistance has resulted from specific point mutations in the dihydropteroate synthase (DHPS) gene. Similar mutations have been observed in P. jirovecii. Studies have consistently demonstrated a significant association between the use of sulfa drugs for PCP prophylaxis and DHPS gene mutations. Whether these mutations confer resistance to TMP-SMX or dapsone plus trimethoprim for PCP treatment remains unclear. We review studies of DHPS mutations in P. jirovecii and summarize the evidence for resistance to sulfamethoxazole and dapsone.
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PMID:Dihydropteroate synthase gene mutations in Pneumocystis and sulfa resistance. 1550 56

Oligoribonucleotides containing 8-oxo-7,8-dihydroguanosine (8-oxoG) and 8-oxo-7,8-dihydro-2'-O-methylguanosine (8-oxoG-Me) were synthesized. The base pairing properties of 8-oxoG and 8-oxoG-Me in oligoribonucleotide in cDNA synthesis by reverse transcriptases were studied. dCMP was preferentially incorporated into the site opposite 8-oxoG or 8-oxoG-Me than into other dNMPs. TMP and dCMP were inserted preferentially into sites opposite 8-oxoG or 8-oxoG by reverse transcriptases. HIV-RT did not incorporate TMP, but RAV2-RT incorporated 50% more TMP than dCMP into the site opposite 8-oxoG. In the site opposite 8-oxoG-Me TMP was substantially incorporated by HIV-RT or RAV2-RT. Thermodynamic analysis of the DNA.RNA heteroduplex containing 8-oxoG revealed that 8-oxoG and 8-oxoG-Me formed base pairs with cytidine and thymidine with similar stability. The thermodynamic parameter (DeltaG degrees ) demonstrated that the formation of duplexes between 8-oxoG or 8-oxoG-Me and cytidine or thymidine is more thermodynamically favorable than with adenosine and guanosine. However, differences in the melting temperature and DeltaG degrees 's of 8-oxoG/dC and 8-oxoG/T were much smaller than between G/dC and G/T. CD spectra showed that DNA . RNA containing 8-oxoG or 8-oxoG-Me duplexes showed similarities between the A-type RNA and B-type DNA conformations.
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PMID:DNA . RNA heteroduplex containing 8-oxo-7,8-dihydroguanosine: base pairing, structures, and thermodynamic stability. 1560 23


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