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

The clinical effectiveness of rifabutin for prophylaxis of disseminated Mycobacterium avium complex infection has recently been demonstrated in HIV-positive patients with low CD4 counts. Rifabutin is a newly marketed, semisynthetic antimycobacterial agent similar to rifampicin (rifampin) in structure and activity. However, rifabutin has important pharmacokinetic differences compared with rifampicin. Rifabutin has relatively low oral bioavailability; about 20% after single dose administration. With long term administration rifabutin induces its own metabolism and the metabolism of some other drugs. The elimination half-life of rifabutin is long (45 hours) but, as a result of a very large volume of distribution (> 9 L/kg), average plasma concentrations remain relatively low after repeated administration of standard doses. In vitro rifabutin is more active against M. avium-intracellulare complex and at least as active against M. tuberculosis as rifampicin. In vivo the advantage of rifabutin is less apparent due to its lower plasma concentrations at equivalent doses. Adverse effects are unusual at the recommended oral dosage of 300 mg/day, but become common as the total daily dose approaches 1 g. Dose-limiting toxicity consists of a polyarthralgia/arthritis syndrome, possibly complicated by uveitis. More clinical studies are needed to establish the role of rifabutin in combination therapy for M. avium-intracellulare complex and other mycobacterial infections.
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PMID:Clinical pharmacokinetics of rifabutin. 773 87

In June 1993, the United States Public Health Service (USPHS) made recommendations for treatment of disseminated Mycobacterium avium complex (MAC) in patients infected with the human immunodeficiency syndrome (HIV). It was suggested that every treatment regimen include either azithromycin or clarithromycin plus one or more of the following drugs: ethambutol, clofazimine, rifabutin, rifampin, ciprofloxacin, or amikacin. This study compares the effect of multiple drug therapy regimens on the survival of patients of the HIV outpatient department of the Medical Center of New Orleans, Louisiana. A retrospective chart review of 122 confirmed cases of MAC was conducted. Three treatment groups were considered: no/monotreatment (n = 40), multitreatment without clarithromycin (n = 32), and multitreatment with clarithromycin (n = 50). Azithromycin, amikacin, and rifabutin were not used in this clinic during the study period. Both multitreatment without clarithromycin (p < 0.03) and multitreatment with clarithromycin (p < 0.005) were significantly protective for survival after adjusting for CD4 cell count at time of diagnosis, nonadherence to treatment, number of concomitant opportunistic infections at diagnosis, and weight loss > 10%. Neither of the groups that received multidrug therapy were significantly less likely to have MAC-related symptoms than the no/mono group at 3 and 6 months postdiagnosis. These findings support the USPHS recommendation for multiple drug treatment either with or without clarithromycin. Prospective controlled clinical trials will clarify the optimal regimen for disseminated MAC disease.
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PMID:Comparison of multiple drug therapy regimens for HIV-related disseminated Mycobacterium avium complex disease. 774 89

Diarrhea, the etiology of which often is obscure, is a major complication of human immunodeficiency virus (HIV) disease. Diarrheogenic bacterial infections (eg, enteropathogenic Escherichia coli) are diagnosed traditionally by stool analysis rather than by examination of endoscopic biopsy specimens. Although E coli rarely have been associated with diarrhea in HIV/acquired immunodeficiency syndrome (AIDS) patients, neither have they routinely been sought. Endoscopic ileal and colorectal biopsy specimens from AIDS-positive patients with chronic diarrhea were analyzed by light and transmission electron microscopy (TEM). The surface epithelium of many large intestinal biopsy specimens previously diagnosed with, for example, nonspecific colitis, regularly showed disarray, degeneration, and necrosis, often with polymorphonuclear neutrophils (PMNs) and eosinophils, irregular cell aggregates, cell shedding, and defects. The crypts were not involved nor were consistent changes noted in the lamina propria. Closer scrutiny of 52 of these biopsy specimens showed gram-negative coliform bacteria intimately associated with histopathology in four distinct patterns. In 22 biopsy specimens, including two from infants, four morphological types of bacilli were observed that adhered to and effaced the brush border in the classic manner with cytoskeletal rearrangement and pedestals. Other bacterial morphologies and/or patterns of epithelial interaction also were observed (ie, thin bacilli intercalated between microvilli [n = 7], loosely associated bacilli [n = 21], and enterocyte invasion by long rods [n = 2]). Three patients also had minor ileal involvement. Infection was greatest in the right colon and coinfections (eg, microsporidia, Mycobacterium avium complex, adenovirus, and especially cytomegalovirus) were documented in 37% (19 of 52) of specimens. Diarrheogenic bacterial infections, some of the E coli type, may be an important cause of diarrhea in HIV disease. Their precise characterization is needed so that stool samples, not endoscopic biopsy specimens, can be used for diagnosis.
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PMID:Diarrheogenic bacterial enteritis in acquired immune deficiency syndrome: a light and electron microscopy study of 52 cases. 775 Sep 32

We present a patient with a very large pericardial effusion due to disseminated Mycobacterium avium complex (MAC) infection with associated bacteraemia and gastroenteritis. He was HIV antibody-positive with a CD4+ lymphocyte count of 10 x 10(6)/l. He complained of fevers, diarrhoea and dyspnoea and an echocardiogram showed a pericardial effusion. Chest X-ray showed progressive enlargement of the cardiac silhouette over a 3-month period. The effusion was drained surgically and antimycobacterial therapy (clarithromycin, clofazamine, rifampicin, ciprofloxacin, amikacin) was initiated. The patient had complete resolution of his pericardial effusion both clinically and radiologically. Three other AIDS patients with pericardial effusions caused by MAC are described in the medical literature, two died of cardiac dysfunction shortly after diagnosis. There is a case described of MAC-related pericardial effusion in a HIV-negative immunocompetent patient which resolved antimycobacterial therapy. MAC should be included in the differential diagnosis of pericardial effusions in AIDS patients. A combination of medical therapy and surgical intervention may give rise to considerable clinical benefit especially if initiated early.
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PMID:Mycobacterium avium: a potentially treatable cause of pericardial effusions. 775 68

To assess the frequency and etiology of fever of uncertain origin (FUO) in patients infected with the human immunodeficiency virus (HIV) and to evaluate the yield of diagnostic procedures used in their evaluation, we reviewed the clinical charts of all patients admitted to an AIDS unit during a 15-month period. FUO was defined by the endurance of a fever (temperature, > 38.2 degrees C) for at least 4 weeks before admission and the uncertainty of diagnosis after 3 days, despite appropriate investigation. Of 580 patients evaluated, 50 (8.2%) had FUO. Patients with FUO were at advanced stages of HIV infection (median CD4+ cell count, 71/mm3), and a vast majority (84%) had previously diagnosed AIDS. A cause of the fever was identified for 44 patients (88%), and infections accounted for 82% of all cases. Tuberculosis (42%), visceral leishmaniasis (14%), and disseminated Mycobacterium avium complex infection (14%) were the most frequent diagnoses. Examination of lymph node aspirates, bone marrow biopsy, and culture of clinical specimens for mycobacteria were the procedures with the highest diagnostic yield. Among 6 patients with fever of no identified etiology, 4 died while febrile, and fever was self-limited in the other 2 patients. FUO is common among patients with advanced HIV infection. Since a cause, usually infection, can be identified in most patients, long-lasting fever should not be attributed to HIV itself.
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PMID:Fever of uncertain origin in patients infected with the human immunodeficiency virus. 779 88

Nanoparticles are known to accumulate in the phagocytic cells of the mononuclear phagocyte system. Therefore, the use of this carrier system for the targeting of antiviral drugs to monocytes/macrophages (MO/MAC) is an attractive concept in the treatment of diseases involving MO/MAC, e.g. infection with HIV. In this study, the ability of macrophages isolated from peripheral blood of healthy blood donors to phagocytose and metabolize human serum albumin microspheres was investigated by transmission electron microscopy. Furthermore, nanoparticles manufactured using human serum albumin or polyhexylcyanoacrylate were loaded with nucleoside analogues (AZT and ddC) and tested for their ability to prevent HIV infection in MO/MAC cultures. Our results demonstrate the effectiveness of this drug-targeting system to one of the major target cells for HIV.
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PMID:Inhibition of HIV in vitro by antiviral drug-targeting using nanoparticles. 780 Sep 48

Disseminated Mycobacterium avium complex (MAC) infection is a common complication of advanced HIV disease that is associated with significant morbidity. After diagnosis of MAC by recovery of organisms from blood or other normally sterile sites, specific treatment with multiple-drug regimens is appropriate and may reduce morbidity. Multiple-drug regimens with agents active against MAC should be employed to reduce the development of drug resistance. Unfortunately, as most clinical trials of anti-MAC agents have lasted 12 weeks or less and have not compared specific agents, the most effective multiple-drug regimen has not been established. The U.S. Public Health Service Task Force on Prophylaxis and Therapy of MAC recommends treatment of disseminated disease with at least two antimycobacterial agents, one of which should be clarithromycin or possibly azithromycin. Ethambutol, which may have an additive or synergistic effect in combination with other anti-MAC agents, is a reasonable second drug. Other agents with activity include rifampin or rifabutin, clofazimine, ciprofloxacin, or parenteral amikacin. A microbiological response may require up to 2 to 8 weeks. The clinical response generally parallels the microbiological response. Rifabutin, which is licensed for prophylaxis of MAC, reduces the incidence of and delays the time to MAC bacteremia. Individuals at highest risk of MAC bacteremia (i.e., CD4+ cell counts of < 75-100 cells/microliters) had the most benefit from rifabutin prophylaxis. Tuberculosis must be ruled out before rifabutin prophylaxis is initiated. Careful observation without prophylaxis is an acceptable alternative for those who are not able to take rifabutin or alternative agents.
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PMID:Disseminated Mycobacterium avium complex disease in patients with AIDS. 781 42

Previous studies from Africa have been unable to identify disseminated Mycobacterium avium complex (MAC) infection in patients with advanced human immunodeficiency virus (HIV) infection. We performed mycobacterial blood cultures and CD4 counts on 48 symptomatic adults with advanced HIV infection admitted to the hospital in Nairobi, Kenya over 4 weeks in 1992. Fourteen patients had mycobacteremia; these patients had significantly lower CD4 counts than the patients with negative cultures (14/mm3 vs. 85/mm3; p < 0.01). Three patients (6%) were bacteremic with M. avium (mean CD4 count, 10/mm3) and 11 (23%) were bacteremic with Mycobacterium tuberculosis complex (MTB) (mean CD4 count, 15/mm3). Thus, M. avium bacteremia was detected significantly less frequently in the study population than MTB bacteremia (p = 0.04). The minimum rate for HIV-associated disseminated M. avium infection in patients admitted to the hospital in Nairobi was estimated to be approximately 1%. Patients with mycobacteremia died or were discharged home sick before the diagnosis was made. Disseminated M. avium does occur in adults with advanced HIV infection in sub-Saharan Africa, but is less common than disseminated MTB.
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PMID:Disseminated Mycobacterium avium infection among HIV-infected patients in Kenya. 783 2

The number of cases with tuberculosis is again increasing in many countries, and recently several nosocomial outbreaks of multidrug-resistant tuberculosis have occurred in the United States. The number of patients with disseminated Mycobacterium avium complex (MAC) infections in AIDS population, and patients with MAC pulmonary disease unassociated with HIV seem to be also increasing. It takes at least 6 to 9 months for an initial treatment of active tuberculosis due to drug-sensitive strains with the standard regimen which includes isoniazid (INH) and rifampicin (RFP). Treatment for the diseases caused by drug-resistant M. tuberculosis and MAC is much more time-consuming and more toxic than for the diseases caused by drug-sensitive strains, and often unsuccessful. For the reasons described above, the developments of new agents with potent antimycobacterial activities are highly desired. The new agents should also be useful for treating patients who have acquired resistance to many of the currently available drugs. In this review the new antimycobacterial drugs are summarized. Some of them have already been used clinically, but many are still in experimental evaluations. 1) Rifamycin derivatives: rifabutin (RBT), KRM-1648 (KRM), rifapentin (RPT), FCE-22250, FCE-22807, CGP-7040, SPA-S-565 and other rifamycin derivatives. New rifamycin derivatives including RBT, KRM have increased in vitro antimycobacterial activities. RBT and KRM are much more active in vitro and in vivo than RFP against both M. tuberculosis and MAC. KRM seems to be more potent than RBT against MAC in experimental studies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[New drugs against tuberculosis and nontuberculous mycobacterial infections: a review]. 783 25

Organisms belonging to the Mycobacterium avium complex (MAC) are common pathogens in immunosuppressed and AIDS patients. This paper reviews the role of cytokines in the pathogenesis of MAC infection. MAC organisms mainly infect monocytes and macrophages, and the effect of HIV infection on susceptibility of macrophages to MAC infection is largely unknown. Both GM-CSF and tumour necrosis factor-alpha can induce mycobacteriostatic/mycobactericidal activity in MAC-infected macrophages. The activity of interferon-gamma on mycobacterial infection appears to be dependent on the type of macrophage: in murine peritoneal and human monocyte-derived macrophages, interferon-gamma does not inhibit the intracellular growth of MAC, whereas in intestinal macrophages interferon-gamma results in inhibition of MAC. Transforming growth factor-beta 1, interleukin-10 and interleukin-6 have all been shown to counteract the immunoactivating cytokines and MAC survival may be due to induction of these inhibitory cytokines within the macrophage. GM-CSF has been given to patients with disseminated MAC infection. Isolated macrophages from these patients demonstrated increased superoxide anion production and enhanced mycobacteriostatic/cidal activity compared with macrophages isolated from the same patients before GM-CSF treatment. These results suggest that GM-CSF may have potential in the treatment of MAC infection.
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PMID:Potential role of cytokines in disseminated mycobacterial infections. 787 49


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