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

Pfizer Inc. will establish a program for the free distribution of fluconazole (Diflucan), a drug used to treat cryptococcal meningitis, known to occur in many people with AIDS, in South Africa. The drug's high cost has been a barrier to treating this often fatal infection. A joint effort by MSF (Doctors Without Borders), TAC (Treatment Action Campaign), ACT UP, and others have spurred the effort.
AIDS Treat News 2000 Apr 07
PMID:Pfizer will donate Fluconazole to South Africa. 1136

Mucocutaneous candidiasis is frequently one of the first signs of HIV infection. Over 90% of patients with AIDS will develop oropharyngeal candidiasis at some time during their illness. Although numerous antifungal agents are available, azoles, both topical (clotrimazole) and systemic (fluconazole, itraconazole), have replaced older topical antifungals (gentian violet and nystatin) in the management of oropharyngeal candidiasis in these patients. The systemic azoles, itraconazole and fluconazole, are generally safe and effective agents in HIV-infected patients with oropharyngeal candidiasis. A concern in these patients is clinical relapse, which appears to be dependent on degree of immunosuppression and is more common following clotrimazole and ketoconazole than following fluconazole or itraconazole. Candida esophagitis is also of concern, since it occurs in more than 10% of patients with AIDS. Fluconazole is an integral part of the management of mucosal candidiasis. A cyclodextrin oral solution formulation of itraconazole has clinical response rates similar to fluconazole and is an effective alternative. In patients with fluconazole-refractory mucosal candidiasis, treatment options include itraconazole, amphotericin B oral suspension, and parenteral amphotericin B.
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PMID:Therapeutic options for the management of oropharyngeal and esophageal candidiasis in HIV/AIDS patients. 1159 Apr 89

A model of orogastric candidosis in SCID mice, which mimics disease seen in AIDS patients, was used to evaluate ravuconazole in comparison with fluconazole for treatment. Mice were infected orally with Candida albicans and received either no treatment or oral treatment once daily for 12 days with 1, 5, or 25 mg of ravuconazole per kg of body weight per day, 5 or 25 mg of fluconazole per kg per day, or diluent (10% dimethyl sulfoxide in 0.5% carboxymethyl cellulose). The numbers of C. albicans CFU in the esophagus, stomach, small intestine, and cecum on day 25 in mice given no treatment and diluent were equivalent. Both doses of fluconazole significantly reduced numbers of CFU in all four tissues but were equivalent to each other. Ravuconazole showed dose-responsive improvement of clearance of CFU. Ravuconazole at 25 mg/kg was superior in reduction of numbers of CFU in all tissues to controls or 25 mg of fluconazole per kg and to other regimens in at least three tissues. Fluconazole at 25 mg/kg cured no infection in any tissue, whereas 25 mg of ravuconazole/kg cleared infection in all tissues from 50% of mice. Ravuconazole has good efficacy and the potential to cure mucosal candidosis in the absence of a functional immune response.
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PMID:Efficacy of ravuconazole in treatment of mucosal candidosis in SCID mice. 1170 20

Since the 1990s, the substantial increase in the rate of Candida glabrata infections has become a serious problem. As most C. glabrata infections arise from the host's endogenous microflora, the present prospective, multicenter analysis included all clinical isolates associated with colonization and with systemic and hematogenous candidiasis. Among 347 C. glabrata isolates, the overall rates of resistance to fluconazole (MIC > or = 64 micro g/ml) and itraconazole (MIC > or = 1 micro g/ml) were 10.7 and 15.2%, respectively, although for half (n = 148) of the itraconazole-susceptible isolates the MICs (0.25 to 0.5 micro g/ml) were in the susceptible-dependent upon dose range. Fluconazole resistance was more common among C. glabrata isolates obtained from centers caring for patients with cancer (MICs at which 90% of isolates are inhibited [MIC(90)s] = 32 micro g/ml) or AIDS (MIC(90)s > 64 micro g/ml) than among C. glabrata isolates from a community-based university medical center (MIC(90)s = 16 micro g/ml) (P = 0.001). Thirty-three bloodstream isolates and those obtained from other body sites had similar in vitro susceptibility profiles. The fluconazole MIC(90)s (< or =16 micro g/ml) for C. glabrata yeast isolates from the gastrointestinal tract were lower than those (> or =64 micro g/ml) for C. glabrata isolates from respiratory and urinary tract samples (P = 0.01). A similar discrepancy for itraconazole was not significant (P > 0.5). We did not observe differences in fluconazole or itraconazole susceptibility profiles among C. glabrata isolates associated with either hematogenous dissemination or colonization. The significant discrepancy in antifungal susceptibility among C. glabrata organisms isolated from hospitals in the same geographic region emphasizes the significance of periodic susceptibility surveillance programs for individual institutions, especially those providing care to patients at risk.
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PMID:Prospective, multicenter surveillance study of Candida glabrata: fluconazole and itraconazole susceptibility profiles in bloodstream, invasive, and colonizing strains and differences between isolates from three urban teaching hospitals in New York City (Candida Susceptibility Trends Study, 1998 to 1999). 1223 57

This article reports on Pfizer's AIDS drug donation to South Africa. The donated drug, Diflucan, treats cryptococcal meningitis, a lethal brain infection that occurs in one out of 10 HIV patients. Its daily dose in South Africa costs about US$15, far more than poor people can afford. The HIV and AIDS Treatment Action Campaign, an advocacy group, had lobbied New York-based Pfizer for a year to reduce the drug's price. The donation offered hope among activists that other pharmaceutical companies would follow suit and offer HIV- and AIDS-related drugs at a discount or for free. After the announcement of the donation, the group is now lobbying Glaxo Wellcome, maker of Zidovudine. The group is asking to make the drug available for free to reduce the risk of vertical transmission. Glaxo Wellcome, however, has no plans of offering Zidovudine for free, although the drug was offered 75% cheaper in developing nations.
AIDS Wkly
PMID:Pfizer donates drug to South Africa's poor. 1229 55

Candida albicans is an opportunistic human fungal pathogen and a causative agent of oropharyngeal candidiasis (OPC), the most frequent opportunistic infection among patients with AIDS. Fluconazole and other azole antifungal agents have proven effective in the management of OPC; however, with increased use of these agents treatment failures have occurred. Such failures have been associated with the emergence of azole-resistant strains of C. albicans. In the present study we examined changes in the genome-wide gene expression profile of a series of C. albicans clinical isolates representing the stepwise acquisition of azole resistance. In addition to genes previously associated with azole resistance, we identified many genes whose differential expression was for the first time associated with this phenotype. Furthermore, the expression of these genes was correlated with that of the known resistance genes CDR1, CDR2, and CaMDR1. Genes coordinately regulated with the up-regulation of CDR1 and CDR2 included the up-regulation of GPX1 and RTA3 and the down-regulation of EBP1. Genes coordinately regulated with the up-regulation of CaMDR1 included the up-regulation of IFD1, IFD4, IFD5, IFD7, GRP2, DPP1, CRD2, and INO1 and the down-regulation of FET34, OPI3, and IPF1222. Several of these appeared to be coordinately regulated with both the CDR genes and CaMDR1. Many of these genes are involved in the oxidative stress response, suggesting that reduced susceptibility to oxidative damage may contribute to azole resistance. Further evaluation of the role these genes and their respective gene products play in azole antifungal resistance is warranted.
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PMID:Genome-wide expression profile analysis reveals coordinately regulated genes associated with stepwise acquisition of azole resistance in Candida albicans clinical isolates. 1265 50

The purpose of this review was to investigate the management of oral candidiasis in HIV/AIDS patients and to evaluate the different guidelines available for its management. A number of topical and systemic antifungal medications are used to treat oral candidiasis in HIV-positive patients. Milder episodes of oral candidiasis respond to topical therapy with nystatin, clotrimazole troches or oral ketoconazole. Fluconazole has been extensively evaluated as a treatment for candidiasis. With HIV-infection, a cure rate of 82% has been achieved with a daily oral dose of 50 mg. Fluconazole was found to be a better choice of treatment for relapsing oropharyngeal candidiasis, resulting in either better cure rates or better prevention of relapse. Intravenous amphotericin B has been found to be effective in azole-refractory candidiasis and is well tolerated. Topical therapies are effective for uncomplicated oropharyngeal candidiasis; however, patients relapsed more quickly than those treated with oral systemic antifungal therapy. Nystatin appeared less effective than clotrimazole and the azoles in the treatment of oropharyngeal candidiasis. Clotrimazole was found to be just as effective for resolution of clinical symptoms as the azoles, except when patient compliance was poor. Fluconazole-treated patients were more likely to remain disease-free during the fluconazole follow-up period than those treated with other antifungal agents.
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PMID:A systematic review of the management of oral candidiasis associated with HIV/AIDS. 1267 66

A review of the partnership between Pfizer Inc. and the South African Ministry of Health to distribute free Diflucan (fluconazole) in the Diflucan Partnership Program (DPP) demonstrates that product donations may be a useful response to AIDS if they are coupled with efforts to build means of drug distribution and enhance professional healthcare capacity to treat patients. Equally important is the creation of a new set of productive working relationships between stakeholders who came to the project with different backgrounds and perspectives, as well as a frankly disparate set of objectives. A decision tree illustrates how these relationships were built into the DPP. This review concludes with a few lessons learned in providing medicines not only to South Africa, but also to the 77 other African countries now participating in the DPP. As the search for new treatments and vaccines continues, increasing access to existing medicines through targeted donations--including training and infrastructure support--is the most practical way for the health community to address the problem of ill health among the poor. In addition to a detailed analysis of the DPP, there is also a discussion of the benefits of a donation program that addresses the AIDS crises on a global scale. This review may serve as a blueprint for establishing programs that are successful in fighting AIDS and improving the lives of millions of people.
J Int Assoc Physicians AIDS Care (Chic)
PMID:Successful public/private donation programs: a review of the Diflucan Partnership Program in South Africa. 1557 10

Opportunistic fungal infections are becoming more frequent complications during cancer therapy, after organ transplantation and in AIDS infections, especially after better control of bacterial infections in immunocompromised patients. Periods of prolonged neutropenia with neutrophil count less than 0.5 x 10(9)/L longer than 7 days, are the most important risk factors for the development of systemic fungal infections. Especially susceptible are the patients during treatment of acute leukemia, or after bone marrow transplantation. The most frequent causing agents of systemic fungal infections are Candida and Aspergillus species, than Cryptococcus neoformans and Mucor. Some other unusual species such Fusarium, Trichosporon, non-albicans Candida species of Candida are becoming more frequent, and is frequently resistant to conventional therapy. The difficulties in early and precise diagnosis of fungal infections, and the lack of adequate and efficient drugs are responsible for the high mortality of immunocompromised patients, even in potentially curable diseases. The recognition of risk factors, introduction of prophylactic measures, application of empirical antifungal therapy, are the procedures for the reduction of morbidity and mortality of invasive fungal infections. Fluconazole administration in prevention of systemic fungal infections, has become the standard approach, especially after bone marrow transplantation, while the oral itraconazole solution, has even more extended activity. Fluconazole appears successful also in the treatment of systemic Candidiasis. Conventional amphotericin-B is still the "gold standard" in the treatment of fungal infections. The new lipid formulations of amphotericin-B, intravenous itraconazole, has an identical efficacy, but are less toxic than conventional amphotericin-B. Several new promising agents are in the stage of clinical investigation like voriconazole, caspofungin, mycafungin and some other.
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PMID:[Systemic fungal infections in immunocompromised patients]. 1570 Jun 80

Cryptococcus neoformans is a haploid environmental organism and the major cause of fungal meningoencephalitis in AIDS patients. Fluconazole (FLC), a triazole, is widely used for the maintenance therapy of cryptococcosis. Heteroresistance to FLC, an adaptive mode of azole resistance, was associated with FLC therapy failure cases but the mechanism underlying the resistance was unknown. We used comparative genome hybridization and quantitative real-time PCR in order to show that C. neoformans adapts to high concentrations of FLC by duplication of multiple chromosomes. Formation of disomic chromosomes in response to FLC stress was observed in both serotype A and D strains. Strains that adapted to FLC concentrations higher than their minimal inhibitory concentration (MIC) contained disomies of chromosome 1 and stepwise exposure to even higher drug concentrations induced additional duplications of several other specific chromosomes. The number of disomic chromosomes in each resistant strain directly correlated with the concentration of FLC tolerated by each strain. Upon removal of the drug pressure, strains that had adapted to high concentrations of FLC returned to their original level of susceptibility by initially losing the extra copy of chromosome 1 followed by loss of the extra copies of the remaining disomic chromosomes. The duplication of chromosome 1 was closely associated with two of its resident genes: ERG11, the target of FLC and AFR1, the major transporter of azoles in C. neoformans. This adaptive mechanism in C. neoformans may play an important role in FLC therapy failure of cryptococcosis leading to relapse during azole maintenance therapy.
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PMID:Cryptococcus neoformans overcomes stress of azole drugs by formation of disomy in specific multiple chromosomes. 2036 72


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