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)

435 hemophiliacs are usually being attended in the La Paz hemophilia Center (Madrid, Spain). 257 (59%) of these patients have been infected by the human immunodeficiency virus (HIV-1) because of human plasma derivate substitution therapy. The infection has been more frequent among the severely affected patients and among the most treated patients. 82% of the infected patients are between 14 and 40 years old. By December 1991, 95 (37%) of 257 seropositive patients have developed full-blown AIDS. The most frequent opportunistic infection they had suffered was esophageal candidiasis. Looking for an evolution marker, we can point that the patients older than 35 years with CD4 levels below 200/mm3 had the worst prognosis. There was no difference in the evolution among the patients aged below 17 and those aged between 17 and 35 years. The amount of concentrate used between 1980 and 1984 did not hold any relation to the evolution. 49 patients (51%) of the 95 suffering from AIDS had died by December 1991. The evolution to the death was unrelated to the patient age, CD4 lymphocyte levels, and amount of substitution therapy. In our opinion, the most valuable marker could be the kind of opportunistic infection or tumor the patient suffers from. Finally, Retrovir has demonstrated to be useful in increasing the survival rate of the patients, but after 36 months of treatment, only 33% of those AIDS patients who began taking it remained alive. Retrovir was also used in asymptomatic patients, and during an average period of time of 15 months, a lesser bone marrow toxicity and a stabilization in CD4 lymphocyte levels could be observed, but this was unable to modify the disease progression in those patients who presented circulating p24 antigen.
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PMID:AIDS and hemophilia: experience in the La Paz Hemophilia Center. 136 77

In the present study the therapeutic efficacy and the side effects of two antiretroviral compounds used in human acquired immunodeficiency syndrome (AIDS) research, 3'-azido-2',3'-dideoxythymidine (AZT, zidovudine, Retrovir) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA), were investigated in the treatment of cats naturally infected with feline immunodeficiency virus (FIV) and cats naturally infected with feline leukemia virus (FeLV). AZT was administered subcutaneously at a dose of 5 mg kg-1 body weight every 12 h and PMEA was administered subcutaneously at a dose of 2.5 mg kg-1 body weight every 12 h during a 3 week hospitalization. The therapeutic efficacy of both compounds was investigated. There was a stronger potency of PMEA than of AZT on the regression of stomatitis in FIV and in FeLV infected cats. In addition, in FIV infection PMEA had a stronger effect on the improvement of the general clinical status. Both antiretroviral compounds were potent agents to improve the immunologic status of FIV infected cats by raising the CD4/CD8 ratio. In FeLV infection PMEA and AZT appeared to reduce antigenemia. The hematological side effects caused by PMEA were severe and stronger than those of AZT. Therefore the advantage of PMEA in clinical and immunologic improvement was diminished by the hematologic disorders, which do not allow long term treatment with this drug in the dose used.
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PMID:Use of two virustatica (AZT, PMEA) in the treatment of FIV and of FeLV seropositive cats with clinical symptoms. 136 8

It is recognized that high-level resistance to 3'-azido-3'-deoxythymidine (AZT, zidovudine, or Retrovir) is conferred by the presence of four mutations in the human immunodeficiency virus (HIV) reverse transcriptase [RT; deoxynucleoside-triphosphate:DNA deoxynucleotidyltransferase (RNA-directed), EC 2.7.7.49] coding sequence. However, a number of clinical isolates have been observed that exhibit high-level resistance but contain only three of the four identified mutations (Asn-67, Arg-70, and Tyr-215). Construction of a molecular clone with this genotype gave rise to only a partially resistant virus, raising the possibility that an additional mutation existed in some clinical isolates. Using an HIV marker rescue system, we have mapped and identified a fifth mutation conferring resistance to zidovudine, namely, methionine to leucine at codon 41 of HIV RT. An infectious molecular clone containing this mutation together with three previously identified mutations in the RT coding sequence yielded highly resistant HIV after transfection of T cells. Direct detection of the fifth mutation in DNA samples from cocultured peripheral blood lymphocytes by the PCR revealed that it occurred relatively early in the development of zidovudine resistance. However, this mutation was only detected after the appearance of the codon 215 change in the RT coding sequence. Identification of this mutation in addition to the other known mutations conferring resistance enables rapid and direct correlation between an RT genotype and sensitivity of the virus.
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PMID:Fifth mutation in human immunodeficiency virus type 1 reverse transcriptase contributes to the development of high-level resistance to zidovudine. 137 86

The development of new antiviral agents has gained increasing momentum. It has kept pace with the identification of specific sites ("targets") in the virus replicative cycle at which potential antiviral drug can interact. The current armamentarium of available antiviral drugs consists of amantadine and rimantadine (against influenza A), ribavirin (against respiratory syncytial virus infection), idoxuridine and trifluridine (against herpetic keratitis), vidarabine and acyclovir (against herpes simplex virus infections), ganciclovir (against cytomegalovirus infections) and Retrovir (against AIDS). Various new compounds have been found which selectively inhibit those viruses [i.e. adenovirus, varicella-zoster virus, thymidine kinase-deficient (TK-) herpes simplex virus strains, and rhinoviruses] that are insensitive or poorly sensitive to the presently available antivirals. Several new compounds have also proven active against human immunodeficiency virus, the causative agent of AIDS; and, as a spin-off of the search for anti-AIDS drugs, new agents may also be expected that are effective against other retrovirus infections as well as hepadnavirus (i.e. hepatitis B virus) infections.
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PMID:New acquisitions in the chemotherapy of viral infections. 216 18

At least 60% of patients infected with the human immunodeficiency virus (HIV) develop neurologic disorders. These may be the direct result of human immunodeficiency virus (HIV) infection, opportunistic infections, neoplastic disorders, or cerebrovascular complications. Neurologic diseases associated with HIV infection include encephalopathy, aseptic meningitis, vacuolar myelopathy, peripheral neuropathy, and myopathy. The pathogenesis of these diseases is not known, but it is likely that they will differ. There is evidence that HIV is the etiologic agent of HIV-associated meningitis and subacute encephalitis, but to date there is little evidence to implicate HIV directly as the cause of vacuolar myelopathy, peripheral neuropathies, and myopathies. The results of preliminary clinical studies suggest that treatment with zidovudine (Retrovir) may cause improvement in some patients.
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PMID:Neurologic disorders associated with HIV infections. 219 51

High-dose interferon alfa (IFN alfa) therapy induces an overall response rate of 25% to 30% in unselected patients with acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma. Up to 50% of patients with relatively preserved immune reactivity respond to treatment. However, when dosages of 20 x 10(6) units or more per day are used to induce responses, constitutional and hematologic side effects may be significant. Therefore, efforts are being made to lower the effective dose of IFN alfa. One effort involves combining IFN alfa with zidovudine (AZT; Retrovir; Burroughs Wellcome, Research Triangle Park, NC). These agents act synergistically to block the multiplication of human immunodeficiency virus (HIV) in vitro. The drugs act at different points in the HIV multiplication cycle, which may explain their synergistic interaction. In addition, AZT enhances certain immune functions that have been correlated with a positive IFN alfa response. Preliminary clinical trials indicate that antitumor responses in Kaposi's sarcoma are seen with dosages of IFN alfa as low as 4.5 x 10(6) units per day when combined with AZT. However, the combination of IFN alfa and AZT may also produce dose-limiting hematologic side effects; these effects may limit the usefulness of the drug combination. Strategies for ameliorating these toxicities through the use of additional agents are discussed.
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PMID:Approaches to interferon combination therapy in the treatment of AIDS. 240 90

There is considerable interest in the potential of human immunodeficiency virus type 1 (HIV-1) to develop drug resistance, especially as 3'-azido-3'-deoxythymidine (Retrovir) is now in widespread clinical use to treat people with AIDS and AIDS-related complex (ARC). To address this possibility, mutations in the HIV reverse transcriptase [deoxynucleoside-triphosphate:DNA deoxynucleotidyltransferase (RNA-directed), EC 2.7.7.49] gene have been introduced by site-directed mutagenesis of cloned constructs in Escherichia coli. Analysis of the recombinant mutant reverse transcriptase from a number of these constructs revealed enzymes that maintained enzyme activity but had a reduced ability to recognize inhibitors such as azidothymidine triphosphate. To assess the infectivity of these mutants, several constructs of proviral HIV clones with mutant reverse transcriptase genes have been made and used to transfect T cells. All five mutants tested have lower infectious potential, suggesting considerable levels of reverse transcriptase activity are required for efficient virus replication. Viable virus recovered from two clones showed decreased sensitivity to the antiviral compound phosphonoformate, thus demonstrating the potential for drug-resistant HIV to replicate. However, although the reverse transcriptase from these mutant viruses showed decreased sensitivity to azidothymidine triphosphate, paradoxically these viruses were hypersensitive to azidothymidine when tested in culture.
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PMID:Infectious potential of human immunodeficiency virus type 1 reverse transcriptase mutants with altered inhibitor sensitivity. 247 34

Two novel, semi-automated assays for the assessment of compounds for activity against human immunodeficiency virus (HIV) are described. One assay uses quantitation of DNA by fluorescence to monitor reversal by test compounds of HIV-induced growth inhibition. The second assay measures the amount of HIV p24 by an indirect immunofluorescent technique. Both assays are sufficiently sensitive to allow multiple sampling of 96-well plates. Intra- and inter-assay variability were within acceptable limits. The two assays provide comparable results for given compounds. Retrovir (3'-azido, 3'-deoxythymidine, AZT) protected MT4 cells from HIV-induced growth inhibition, and inhibited the production of HIV p24. Consistent with the results of others, the anti-HIV potency of AZT was dependent on the concentration of the infecting virus. Interestingly, AZT-protected, HIV-infected MT4 cells grew faster than mock-infected MT4 cells, and inclusion of Interleukin 2 in the assay eliminated this effect.
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PMID:Anti-HIV compound assessment by two novel high capacity assays. 249 28

The objectives of this open-labeled, multiple-dose, three-way-crossover trial were to evaluate the safety and tolerance of zidovudine (Retrovir) oral syrup and to assess the bioequivalence of this formulation relative to zidovudine solution and capsule formulations in human immunodeficiency virus-infected patients. Over the 7-day study, 12 adult male subjects received 12 administrations each of the capsule, solution, and syrup formulations every 4 h (six times daily) in a randomized sequence. Frequent blood samples were collected over the 4-h period after dose 12 was administered. Zidovudine concentrations in plasma were determined by a specific and sensitive radioimmunoassay. Results from statistical analyses indicated that all three formulations were bioequivalent with respect to systemic availability (area under the time-concentration curve) and that the syrup was also equivalent to the solution with respect to the maximum peak concentration in serum. The lower relative maximum peak concentration in serum (approximately 81%) and small delays in time to peak concentration (less than 30 min) of the capsule formulation as compared with the liquid formulations are thought to be due to the additional processes of disintegration and dissolution associated with capsule administration. All three preparations were well tolerated during the 7-day study.
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PMID:Bioequivalence assessment of zidovudine (Retrovir) syrup, solution, and capsule formulations in patients infected with human immunodeficiency virus. 258 46

Zidovudine (Retrovir) is the only drug found to be useful for managing human immunodeficiency virus (HIV) infection in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. The drug is virostatic, ie, it prevents replication of HIV by inhibiting the enzyme reverse transcriptase. Zidovudine is well tolerated and provides short-term benefits by improving the quality of life and extending survival time. It is expensive and can be toxic, however, so its use requires close supervision. Zidovudine at present is approved only for patients with documented Pneumocystis carinii pneumonia or with a CD4 count below 200/mm3. Other probable indications include HIV wasting syndrome, HIV dementia complex, oral candidiasis, Kaposi's sarcoma, the presence of early markers of HIV infection, and HIV-related symptomatic thrombocytopenia. A stepwise approach to initiating zidovudine therapy should include detailed counseling and close surveillance.
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PMID:Zidovudine for treating AIDS. What physicians need to know. 266 55


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