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

The objective of this study was to evaluate the influence of protease inhibitor therapy on the rate of progression and survival of 17 AIDS patients with stable Cytomegalovirus retinitis, who were receiving anti-CMV therapy. CD4+ count, HIV load, and CMV antigenemia assay were determined at baseline, at the first month, and every 3 months thereafter. Median CD4+ count increased from 11 to 87 cells/mm3, and median HIV RNA level decreased from 4.96 to 3.28 log10 copies/ml, after 6 months on therapy. Although 9 patients (53%) relapsed in a median time of 97 days (range, 15-152 days), no further episodes were observed during a median follow-up of 17 months (range, 5-18 months). Thus, the probability of remaining free of relapse was twofold higher than that observed in matched patients who did not receive protease inhibitors. Median CD4+ count at the 3rd month was higher in those individuals who went on to progress (p = .03), and a positive result to a CMV antigenemia test was associated with progression of retinitis (relative hazard, 4.45; p = .04). Survival rate was 94% at 17 months (89% increase). Therefore, protease inhibitor therapy reduces retinitis progression and improves survival. However, the immunologic response may not provide initial sufficient protection to avoid, or even may play a role on, early CMV progression.
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PMID:Improved outcome of cytomegalovirus retinitis in AIDS patients after introduction of protease inhibitors. 976 21

Adenoviruses (AdV) cause diseases that range from localized, self-limited illnesses to fatal infections in immunocompromised patients. Culture is assumed to be sensitive but requires viable virus and up to 3 weeks for detection, and it can be inhibited by bacterial contamination. A new PCR method amplifying a region of the hexon gene was developed in order to detect AdV in urine more rapidly and with greater sensitivity than obtainable by culture technology. All 18 serotypes tested were detected. Quantitatively, with optimized urine processing, AdV PCR detected 0.2 PFU/ml (serotype 11) and 10 DNA copies/ml (serotype 2). Serially collected urine samples from human immunodeficiency virus (HIV)-infected patients with concurrent cytomegalovirus retinitis were divided into three groups: AdV culture-positive samples, AdV culture-negative or bacterially contaminated samples from patients with a history of AdV culture-positive urines, and AdV culture-negative samples from patients without a history of AdV culture positivity. Urine samples from healthy adults were also tested by culture and PCR to screen for asymptomatic shedding. Amplification was assessed with and without prior DNA purification. AdV was detected by PCR in 90% of culture-positive urines (100% of unclotted samples, e.g., those culture positive after storage for PCR testing), 71% of culture-negative or bacterially contaminated urines from AdV-infected patients, and 28% from AdV culture-negative patients. Healthy volunteers were culture negative for AdV, and 96% were PCR negative. The new AdV PCR method is rapid and sensitive and can detect viral DNA in samples for which culturing is problematic. The role of AdV replication during HIV infection merits further investigation with sensitive tools such as PCR.
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PMID:PCR method for detection of adenovirus in urine of healthy and human immunodeficiency virus-infected individuals. 977 86

A 36-year old male with a three year history of HIV infection and more recently, CMV retinitis, had several episodes of polyradiculitis with severe bilateral leg pain and urinary retention which resolved slowly over several months. He then presented with high fevers and severe dysphagia with dehydration. Examination showed oral thrush, dyarthric speech and mild memory impairment. Fundoscopic exam showed CMV retinitis and HIV retinopathy. Further examination revealed other cranial nerve signs and leg weakness. MRI scans showed several contrast enhancing abnormalities of cranial nerve roots. The patient died from massive barium aspiration. At autopsy the brain showed multiple CMV cranial neuritis, CMV polyradiculitis and CMV ventriculo-ependymitis. While spinal nerve root involvement by CMV may occur in up to 1% of AIDS patients, involvement of cranial nerves is unusual and CMV infection of multiple cranial nerves is distinctly rare.
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PMID:Case of the month: May 1998--a patient with HIV infection and multiple cranial neuritis. 980 88

We describe a 46-year-old man in whom retinitis was diagnosed as his initial HIV and AIDS defining illness. A diagnosis of CMV infection was made based on the clinical appearance of the fundus and confirmed by DNA polymerase chain reaction (PCR) on his vitreous biopsy. His CD4+ T lymphocyte count at the time was 580 x 10(6)/l (16%) with a CD4:CD8 ration of 0.28. He had a splenectomy following trauma more than 20 years earlier. He responded very well to intravenous and oral ganciclovir and remains recurrence-free almost 2 years later. This case and others highlight two issues: (i) CMV retinitis in HIV positive is not confined to those with very low CD4+ T lymphocyte counts; (ii) previous splenectomy may have an impact on CD4+ cell numbers and function.
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PMID:Cytomegalovirus retinitis, human immunodeficiency virus antibody positivity and normal T helper cell numbers. 982 Oct 96

The association of the Epstein-Barr virus with human immunodeficiency virus-associated primary central nervous system lymphomas is well known. We describe a pediatric patient infected with human immunodeficiency virus who developed a lesion in the central nervous system that appeared to be histologically reactive and that proved to be an Epstein-Barr virus-associated monoclonal B-cell lymphoproliferative disorder by molecular analysis. An 8-year-old girl was diagnosed with vertically transmitted human immunodeficiency virus infection at age 5, for which she was treated empirically with a combination of zidovudine and didanosine. At the age of 7 years, during evaluation for entry into an antiretroviral protocol, a single hypodense frontal lobe lesion was identified by computed tomography. After unsuccessful treatment for presumed toxoplasmosis and progressive neurologic deterioration, a stereotactic brain biopsy was performed. Although the biopsy contained a polymorphic lymphoid infiltrate that appeared to be cytologically reactive, polymerase chain reaction and in situ hybridization studies revealed a monoclonal Epstein-Barr virus-associated B-cell lymphoproliferative disorder, which was reminiscent of polymorphic B-cell hyperplasia observed in the setting of immunosuppression following organ transplantation. Postoperative therapy included steroids and antiretroviral therapy. The lesion decreased slightly in size, and the child's neurologic status was relatively unremarkable for 5 months. Subsequently, she developed cytomegalovirus retinitis, progressive encephalopathy, and died with pancytopenia. This case represents a newly described manifestation of Epstein-Barr virus-associated lymphoproliferative disorder, a diagnosis that should be considered in patients with neurologic symptoms and immunodeficiency. In addition, this case exhibited histologic features reminiscent of posttransplant lymphoproliferative disease, a histologic pattern that to our knowledge has not previously been reported in the setting of acquired immunodeficiency syndrome.
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PMID:Low-grade monoclonal Epstein-Barr virus-associated lymphoproliferative disorder of the brain presenting as human immunodeficiency virus-associated encephalopathy in a child with acquired immunodeficiency syndrome. 992 43

Cidofovir and adefovir are members of a new class of antiviral compounds. They are acyclic phosphonate analogues of deoxynucleoside monophosphates. Both compounds undergo intracellular activation to form diphosphates that are potent inhibitors of viral DNA polymerases. Cidofovir has broad spectrum antiviral activity against herpesviruses, papillomaviruses and poxviruses, whereas adefovir has potent activity against retroviruses and certain DNA viruses, including herpesviruses and hepadnaviruses. Intravenous cidofovir is approved for treatment of cytomegalovirus retinitis in patients with AIDS. Cidofovir and adefovir are dianionic at physiological pH and have low oral bioavailability in animals and humans. After intravenous administration to HIV-infected patients, the pharmacokinetics of both drugs are independent of dose and are consistent with preclinical data. Systemic exposure is proportional to the intravenous dose and both drugs are cleared by the kidney and excreted extensively as unchanged drug in the urine. Intracellular activation of a small fraction (< 10%) of the dose by cellular kinases leads to prolonged antiviral effects that are not easily predicted from conventional pharmacokinetic studies. The observed rate of elimination of cidofovir and adefovir from serum may not reflect the true duration of action of these drugs, since the antiviral effect is dependent on concentrations of the active phosphorylated metabolites that are present within cells. For both drugs, > 90% of an intravenous dose is recovered unchanged in the urine over 24 hours. Metabolism does not contribute significantly to the total clearance of either drug. Concomitant oral probenecid decreases both the renal clearance of cidofovir and the incidence of nephrotoxicity, presumably by blocking its active tubular secretion. This is the basis of the clinical use of concomitant probenecid as a nephroprotectant during cidofovir therapy. Subcutaneous administration produces exposure equivalent to that following intravenous administration. Drug interaction studies with cidofovir are ongoing, but there is no evidence of an interaction between zidovudine and either cidofovir or adefovir. Clearance of cidofovir in patients with renal impairment showed a linear relationship to creatinine clearance. The low oral bioavailability of adefovir has led to the development of an oral prodrug, adefovir dipivoxil, currently in development for the treatment of HIV and hepatitis B infections.
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PMID:Clinical pharmacokinetics of the antiviral nucleotide analogues cidofovir and adefovir. 1009 59

Cytomegalovirus (CMV) is responsible for the most common viral opportunistic infection in persons with acquired immunodeficiency virus syndrome (AIDS). Clinical disease due to CMV has been recognized in up to 40% of patients with advanced HIV disease. The most common presentation is retinitis, although colitis, esophagitis, pneumonitis and neurological disorders are also reported frequently. CMV retinitis is usually diagnosed clinically, and serological testing for CMV immunoglobulin is useful to support the diagnosis. Parts of the gastrointestinal tract (esophagus and colon) are the most common extraocular sites of CMV infection in AIDS patients. Therapy with systemic agents, including intravenous ganciclovir, intravenous foscarnet, and intravenous cidofovir, is effective. Ganciclovir is associated mainly with hematological toxicity, while foscarnet and cidofovir are nephrotoxic. Intravitreal injections with these antiviral agents are also effective, but inconvenient, and there is a need for repeated injections. Intraocular implants that slowly release ganciclovir have been effective for both acute therapy and long-term maintenance, but the occurrence of contralateral ocular and extraocular disease is a serious concern. New agents, as for example an anti-sense agent against CMV, appear promising.
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PMID:Cytomegalovirus infection in patients with HIV infection. 1010 Apr 16

The diagnosis of the ocular manifestations of AIDS is based initially on the clinical appearance of the lesions. However, retinal and choroidal lesions in AIDS patients are frequently the manifestation of disseminated disease. In one autopsy series, 15 of 18 patients with infectious choroiditis died of systemic infection by the same organism causing the choroiditis. Despite the fact that more than 90% of posterior segment infections in AIDS patients are caused by CMV, careful examination with appropriate consideration of differential diagnosis is necessary in all cases in which a classic pattern of CMV retinitis is not seen. Extensive history taking, discussion with the primary care physician, and the appropriate systemic work-up can greatly facilitate the diagnosis of the most likely cause of the apparent opportunistic infection. It is important to remember that noninfectious causes of HIV-related retinal disease can have a similar clinical pattern as infectious causes. In particular, physicians must be careful not to confuse early CMV retinitis with HIV-related noninfectious retinal vasculopathy, the most common retinal finding in patients with HIV disease. In a patient with multifocal superficial lesions in the posterior pole, particularly if the CD4+ count is more than 100 cells/microL, reevaluation rather than immediately initiating therapy may prevent the inadvertent commitment to chronic therapy implicit in a diagnosis of CMV retinitis.
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PMID:Noncytomegalovirus-related chorio-retinal manifestations of the acquired immunodeficiency syndrome. 1015 26

The purpose of this study was to determine the magnitude of the difference in patient preference/utility for intravenous (i.v.) ganciclovir compared with oral ganciclovir for maintenance treatment of cytomegalovirus (CMV) retinitis. We used a cross-sectional, interviewer-administered time trade-off (TTO) exercise with hypothetical health state descriptions, based upon data from clinical trials and the published literature. The study was conducted in a private clinic in Sydney Australia, specialising in the care of people with HIV. A total of 80 individuals with HIV infection who had not developed AIDS were administered the TTO instrument. The main outcome measure was the difference between each respondent's utility score for oral and i.v. ganciclovir maintenance therapy. When the 80 HIV-positive patients were presented with information on drug efficacy, adverse effects and mode of administration, 60 (75%) preferred oral ganciclovir, 4 patients preferred i.v. ganciclovir, and 16 were indifferent. The median utilities were 0.837 (oral ganciclovir) and 0.475 (i.v. ganciclovir). The difference in rankings was statistically significant by Wilcoxon's signed-ranks test (Z = -6.69, p < 0.00005). The median utility scores suggest that, all other things being equal, individuals with HIV infection would prefer an oral formulation of ganciclovir to i.v. administration in the event of CMV retinitis infection.
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PMID:A utility assessment of oral and intravenous ganciclovir for the maintenance treatment of AIDS-related cytomegalovirus retinitis. 1016 62

Cytomegalovirus retinitis, an opportunistic infection caused by the herpesvirus cytomegalovirus, is a major cause of illness in patients with advanced AIDS. As infected patients require long term drug treatment to delay disease progression and minimise loss of vision, the disease is associated with substantial treatment costs which considerably increase overall expenditure on AIDS-related health care. During the last decade, intravenous ganciclovir has been a mainstay of treatment for patients with cytomegalovirus retinitis. However, notwithstanding its demonstrated efficacy as maintenance therapy for this condition, long term intravenous drug administration is both inconvenient and uncomfortable for many patients. Moreover, neutropenia and catheter-related infections have been reported commonly in patients receiving ganciclovir via the intravenous route. To overcome the limitations of intravenous ganciclovir, an oral formulation of the drug has been developed for use as maintenance therapy. In comparative clinical trials, both intravenous and oral ganciclovir maintenance therapy slowed disease progression and preserved visual acuity in patients with stabilised cytomegalo-virus retinitis, although there was evidence that the intravenous formulation was more effective in terms of delaying recurrence of active disease. This suggests that oral ganciclovir use should be limited to the treatment of patients without evidence of immediately sight-threatening cytomegalovirus retinitis. Three published cost analyses, which were based on efficacy and tolerability data derived from 2 randomised, comparative clinical trials, have shown that oral ganciclovir maintenance therapy offers cost advantages over intravenous maintenance therapy, despite the higher acquisition cost of the oral formulation. The higher overall costs of intravenous maintenance treatment, compared with oral therapy, were attributed to higher drug administration and adverse event treatment costs. In one analysis, estimated lifetime treatment costs of oral maintenance therapy were 25.2% lower than those of intravenous maintenance treatment. As yet, no formal cost-effectiveness evaluations of oral and intravenous ganciclovir have been published. Few published data are available regarding the relative effects of intravenous and oral ganciclovir on quality of life. However, in a health state utility analysis, there was a large overall preference among HIV-infected individuals for oral over intravenous maintenance treatment. In conclusion, oral ganciclovir appears to be a cost-saving and patient-preferred alternative to its intravenous counterpart for the maintenance therapy of AIDS patients with stabilised cytomegalovirus retinitis in whom there is no evidence of sight-threatening disease.
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PMID:Ganciclovir. A pharmacoeconomic review of its use as intravenous or oral maintenance therapy in the management of cytomegalovirus retinitis in patients with AIDS. 1016 72


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