Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The DNA polymerase of human herpes viruses, including cytomegalovirus (CMV), and the reverse transcriptase of human immunodeficiency virus (HIV) are selectively inhibited in vitro by the pyrophosphate analogue foscarnet. Inhibition is reversible on withdrawal of foscarnet and additive or synergistic effects have been demonstrated in vitro with other antiviral drugs, including ganciclovir and zidovudine. Foscarnet appears to have negligible effects on host enzymes and cells. Complete or partial clinical resolution of ocular symptoms is obtained in more than 89% of patients with acquired immunodeficiency syndrome (AIDS) and CMV retinitis during foscarnet induction therapy, but relapse occurs soon after ceasing treatment. Maintenance treatment given daily can extend the period of remission considerably. Foscarnet and ganciclovir monotherapy had similar efficacy in the treatment of CMV retinitis in patients with AIDS in several studies, and have been used concomitantly in immunocompromised patients with recalcitrant CMV infections. In 1 trial, patients receiving foscarnet survived for significantly longer than those receiving ganciclovir. Foscarnet has been used successfully in the treatment of limited numbers of immunocompromised patients with CMV-associated gastrointestinal (improvement in over 67% of patients) and other infections. Aciclovir-resistant herpes simplex infections in immunocompromised patients have also been treated successfully with foscarnet. Almost 90% of a foscarnet dose is excreted in the urine. Reversible nephrotoxicity is common during foscarnet therapy, but may be reduced by dosage adjustment and adequate hydration. Anaemia, nausea and vomiting, disturbances in electrolyte levels and genital ulceration have also been associated with administration of the drug. The different tolerability profiles of foscarnet and zidovudine facilitate the use of these agents in combination in patients with AIDS and CMV infection; whereas ganciclovir, like zidovudine, is associated with dose-limiting haematological toxicity. The apparent survival benefits seen in these patients when receiving foscarnet and zidovudine (possibly linked to synergy between zidovudine and foscarnet and/or the inherent anti-HIV activity of foscarnet), appear to offer potentially important advantages for foscarnet over ganciclovir in the treatment of selected patients with AIDS and CMV infections.
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PMID:Foscarnet. A reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic use in immunocompromised patients with viral infections. 752 25

Virological investigations for herpes simplex virus (HSV), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) were performed in nine patients of acute retinal inflammation. Serum samples of all the patients were assayed for IgG and IgM antibodies to HSV, CMV and EBV. Vitreous fluid (VF) from 5 patients was tested by immunofluorescence and culture for detection of HSV and CMV. In four patients, VF was also assayed for IgG and IgM antibodies to HSV and CMV. HSV was shown to be the etiological agent in 3 patients with acute retinal necrosis (ARN) syndrome and in one patient with multifocal retinitis. CMV was the causative agent in one patient of ARN and 1 patient with clinically diagnosed CMV retinitis. Evidences of infection with these three viral agents could not be obtained in one patient with clinical diagnosis of CMV retinitis who tested positive for antibody to human immunodeficiency virus 1. All other patients were HIV negative. Identification of the causative viral agent of acute retinal inflammations may help an ophthalmologist to institute specific therapy particularly for HSV and CMV infections.
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PMID:Investigations in the virological etiology in acute retinal inflammation. 767 32

A phase I/II study evaluated the pharmacokinetics, tolerability, and antiviral activity of oral ganciclovir in persons infected with human immunodeficiency virus (HIV). Oral bioavailability ranged from 2.6% to 7.3%. The mean maximum serum concentration achieved at 1000 mg every 8 h was 1.11 micrograms/mL, and mean trough level was 0.54 microgram/mL. The time to maximum serum drug concentration was 1.0-2.9 h, with a serum half-life of 3.0-7.3 h, suggesting prolonged oral absorption. Serious adverse events were uncommon. Decreased cytomegalovirus (CMV) shedding was observed from all sites. The median days (by dosage) to retinitis progression assessed by retinal examination after initiation of oral ganciclovir were 62 (1000 mg every 8 h), 148 (500 mg every 3 h), 75 (750 mg every 3 h), 148 (1000 mg every 3 h), and 139 (2000 mg every 8 h). Thus, oral ganciclovir has pharmacokinetic, toxicity, and antiviral profiles that may prove beneficial for both maintenance therapy of CMV retinitis and prevention of CMV disease in HIV-infected persons.
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PMID:Pharmacokinetic, safety, and antiviral profiles of oral ganciclovir in persons infected with human immunodeficiency virus: a phase I/II study. AIDS Clinical Trials Group, and Cytomegalovirus Cooperative Study Group. 776 76

Foscarnet inhibits human immunodeficiency virus (HIV) replication in vitro and decreases p24 antigenemia in patients with cytomegalovirus (CMV) retinitis. To evaluate the effect of foscarnet on HIV replication, HIV RNA was quantitated in 17 patients before and during foscarnet therapy. Fifteen patients had CMV retinitis, 1 had CMV encephalitis, and 1 had intractable zoster. A decrease in HIV RNA was observed in 16 of 17 patients. Before the introduction of foscarnet, mean HIV RNA was 5.82 +/- 0.24 log RNA/mL and, after a median of 13 days of therapy, mean HIV RNA was 5.30 +/- 0.27 log RNA/mL (P < .001). Among patients with detectable p24 antigen at baseline, a significant decrease was observed (P = .017). This decrease in HIV RNA demonstrates that foscarnet is a potent antiretroviral drug.
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PMID:Foscarnet decreases human immunodeficiency virus RNA. 779 16

Human cytomegalovirus (CMV) DNA copy number in white blood cells from both human immunodeficiency virus (HIV)-seronegative and HIV-seropositive patients was amplified from the immediate-early region of CMV DNA and quantified by colorimetric detection of the hybridization of the amplification product to a detector oligonucleotide probe in microtiter wells. By Mann-Whitney U test, significantly higher (P < .05, two-tailed) copy numbers of CMV DNA were detected in HIV-seropositive patients with retinitis than in either patients with < 100 CD4 cells/mm3 and no symptomatic CMV disease or HIV-seropositive patients with > 100 CD4 cells/mm3. By prospective monitoring for increases in CMV DNA copy number, it may be possible to identify HIV-seropositive patients who are at imminent risk for development of symptomatic CMV retinitis.
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PMID:Quantitation of human cytomegalovirus DNA from peripheral blood cells of human immunodeficiency virus-infected patients could predict cytomegalovirus retinitis. 779 58

We report the clinical course of cytomegalovirus (CMV) retinitis associated with acquired immunodeficiency syndrome (AIDS) from the initial onset. The patient was a 40-year-old human immunodeficiency virus antibody-positive male with hemophilia A. He was diagnosed as having AIDS on the basis of pneumocystis carinii pneumonia. Ophthalmoscopic examination disclosed a small white punctate lesion at the macular area in his right eye. Because the lesion enlarged gradually with hemorrhages, it was suspected to be CMV retinitis. However, further examination was impossible due to his severe general condition. He died five months later and the autopsy disclosed disseminated CMV infection. Ocular histopathological examination revealed CMV retinitis. The earliest sign of CMV retinitis is supposed to be a white punctate retinal lesion, which becomes a small white patchy lesion resembling a cotton-wool spot. It may gradually progress to diffuse retinal involvement, frequently associated with hemorrhages.
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PMID:[Early cytomegalovirus retinitis]. 782 12

HLA phenotype and immune responses to CMV were studied to determine whether the subset of AIDS patients who developed CMV retinitis were immunogenetically or immunologically predisposed. CMV retinitis develops in approximately 28-35% of AIDS patients and CMV encephalitis develops in 40% of those with retinitis, often leading to death. T-cell proliferation responses to CMV and HIV were assayed prospectively in individuals enrolled in a longitudinal study at the HIV Neurobehavioral Research Center (HNRC) in San Diego. Seventy-three participants, at various stages of disease, have been HLA typed and followed, clinically and immunologically, for up to 5 years. Six HIV infected individuals who eventually developed CMV retinitis, and were assayed prospectively, had a history of low T-cell proliferation to CMV antigens before they were profoundly immunosuppressed. All 10 individuals with CMV retinitis had at least one of three HLA alleles (or combinations): A2B44 (p = 0.02), B51(p = 0.02), or DR7 (p = 0.01) (collective p value = 0.007). Three of the 10 had two or more of these alleles. Of AIDS patients with CD4 counts below 100 and actively at risk for retinitis, 7/15 with A2B44,51, or DR7 have developed retinitis compared to 0/13 without these HLA alleles (relative risk = 23.8). All 4 patients with these alleles who have died, had retinitis. These results suggest that HIV infected individuals with HLA phenotypes A2B44, B51, and DR7 have low T-cell immune responses to CMV and are predisposed to CMV retinitis and encephalitis as immunodeficiency progresses.
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PMID:CMV-specific immune responses and HLA phenotypes of AIDS patients who develop CMV retinitis. HNRC Group. HIV Neurobehavioral Research Center. 787 1

Human immunodeficiency virus (HIV)-infected patients at risk for symptomatic human cytomegalovirus (CMV) infection were studied for serum antibody to CMV glycoproteins gH and gB. Antibody titers to gB in HIV-seropositive patients, irrespective of CD4 cell counts or presence of CMV retinitis, were significantly higher than titers in HIV-seronegative, CMV-seropositive patients but were comparable to titers detected in HIV-seronegative patients with CMV mononucleosis. In contrast, antibody to gH was rarely detected in HIV-seropositive patients with CD4 cell counts > 100/mm3 compared with patients with counts > 100/mm3. The inability to detect gH antibody at a time of high risk for symptomatic CMV retinitis suggests that immune intervention with either gH-specific vaccine or passive immunotherapy may benefit HIV-infected persons at risk for symptomatic CMV disease.
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PMID:Deficiency in antibody response to human cytomegalovirus glycoprotein gH in human immunodeficiency virus-infected patients at risk for cytomegalovirus retinitis. 791 50

We evaluated 49 paired cerebrospinal fluid (CSF) and serum samples of 35 patients infected with the human immunodeficiency virus type 1 (HIV-1) for laboratory evidence of cytomegalovirus (CMV) infection. The patients were grouped according to clinical criteria as probable CMV encephalitis/polyradiculomyelitis, CMV retinitis, cerebral toxoplasmosis, progressive multifocal leukoencephalopathy, HIV-1-related cognitive/motor complex, HIV-1-associated myelopathy, and other neurological diseases. Paired CSF and serum samples were analysed for CMV deoxyribonucleic acid (DNA) by polymerase chain reaction (PCR), quantitative intrathecal synthesis of immunoglobulin G (IgG) antibodies specific for recombinant phosphoprotein 150 (pp150) of CMV and CMV-specific serum IgM. Intrathecal synthesis of pp150-specific IgG was detected in 26% of patients (9/35), serum IgM was found in 23% of patients (8/35), and PCR of CSF was positive in 11% of patients (4/35). Detection of CMV-specific DNA in CSF preceded the intrathecal antibody synthesis in three patients for whom serial samples were available. PCR results of the CSF became negative in one patient with CMV polyradiculomyelitis after successful therapy with 9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl] guanine (DHPG). PCR has a higher diagnostic specificity in the acute phase of CMV infection than intrathecal antibody synthesis. The serum IgM response to CMV cannot be used to monitor a compartmentalized immune response in the central nervous system while an intrathecal immune response seems to be associated with recovery either spontaneously or as a result of treatment.
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PMID:Comparative analysis of intrathecal antibody synthesis and DNA amplification for the diagnosis of cytomegalovirus infection of the central nervous system in AIDS patients. 793 40

The high sensitivity of nested polymerase chain reaction (PCR) offers the possibility of rapid detection of cytomegalovirus (CMV) DNA in serum. Five consecutive serum samples were examined from 52 human immunodeficiency virus (HIV)-seropositive patients (19 of whom had clinically presumed diagnosis of CMV chorioretinitis). Presence of CMV DNA in serum was shown to precede development of clinical disease. Eleven patients who developed chorioretinitis were positive for CMV DNA in serum samples obtained 3 months before clinical disease, and 3 retinitis patients who initially were negative for CMV DNA became positive with the onset of clinical retinitis. In contrast, 29 of 33 HIV-seropositive subjects without clinical CMV chorioretinitis and matched with respect to age and CD4 T cell numbers were negative for CMV DNA in all 5 serum samples. Thus, the presence of CMV DNA in serum analyzed by PCR is a good predictive marker of CMV retinitis in HIV-seropositive subjects. A positive PCR results supports the clinical diagnosis and may be useful for monitoring response to antiviral treatment.
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PMID:Detection of cytomegalovirus DNA in serum correlates with clinical cytomegalovirus retinitis in AIDS. 776 20


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