Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dr. Yuan Chang and her research group believe they have fulfilled the epidemiological criteria for establishing the KSHV (herpes virus) as the cause of Kaposi's Sarcoma (KS), but Dr. Gallo and others still question the virus's role. If KS is caused by KSHV, there is a possibility that an antiviral drug may have a therapeutic effect. Foscarnet, in one open-label study of five people with KS, proved to be effective in three of the cases by causing a remission and even clearing external (and in one case internal) lesions for more than a year after just one or two brief courses. Another retrospective analysis of 20,228 showed people with HIV/AIDS treated with foscarnet were 70 percent less likely to develop KS. Such research evidence warrants further study; one open-label trial for 25 people is recruiting. Call Clare Kenny or Lorrie Jondreau at (212) 263-5244 for more information.
 ...
PMID:KS virus controversy. 1136 55

Eye problems are a significant concern for HIV-positive patients, in whom CMV blindness and vision loss is a devastating side effect. CMV retinitis is the most common eye disease in people with HIV, affecting up to 45 percent of people with AIDS. CMV retinitis is treated with oral or intravenous ganciclovir, although some patients have difficulty absorbing the drug, and an eye implant has been developed. Foscarnet is also used in combination therapy. The Food and Drug Administration (FDA) recommends beginning prophylaxis when CD4 counts drop below 50.
 ...
PMID:The eyes have it, too. 1136 23

Varicella zoster virus (VZV) infections in human immunodeficiency virus (HIV)-infected patients are known to have a different disease spectrum from that seen in other types of patients. Varicella in children with HIV infection is likely to be more serious than in otherwise healthy children and routine antiviral therapy is recommended. There is evidence that the development of varicella in HIV-infected children is not associated with progression to AIDS, suggesting that it may be safe to immunize HIV-infected children with live attenuated varicella vaccine. There are no published data on varicella in HIV-infected adults, however, probably because most adults have already experienced varicella prior to HIV infection. Zoster in HIV-infected children differs somewhat from that in HIV-infected adults. In particular, HIV-infected children who develop varicella in the setting of severe immunodeficiency are at an especially high risk to develop zoster. Given the low rate of toxicity of aciclovir as well as its ease of administration and its efficacy in hastening the healing of VZV infections, prompt treatment with this antiviral agent is recommended for both HIV-infected children and adults. Foscarnet should be used for zoster that is strongly suspected or proven to be caused by aciclovir-resistant VZV. Patients with HIV for whom there is no evidence of significant immunosuppression and who have not had varicella should be immunized with live attenuated varicella vaccine as a preventative measure for both varicella and zoster. It is hoped that immunization of VZV seropositive HIV-infected patients will decrease the incidence of zoster. Studies to determine this are under way.
 ...
PMID:Prevention and treatment of VZV infections in patients with HIV. 1186 15

Two different enzyme assays, both based on the interaction of native reverse transcriptase (RT) and 3'-azido-2',3'-deoxythymidine triphosphate (AZT-TP), were used to characterize the enzymes from 18 HIV-1 isolates with decreased sensitivity to AZT in cell culture. The first assay, which measures the balance between incorporation and excision of AZT monophosphate in the presence of dNTP substrate (in terms of IC(50)), gave an approx. 9-fold variation in sensitivity to AZT-TP. There was a correlation between the IC(50) values and the sensitivity of the corresponding virus to AZT in cell culture (r=0.60, P<0.01). The second assay, which was designed specifically for measurement of chain termination in the absence of dNTP substrate (as the concentration of AZT-TP giving 50% residual primer function, or CT(50)), revealed a more than 600-fold difference between the different isolate RTs. For the majority of enzymes there was a strict correlation between the results from the two assays; however, four isolates exhibited significantly higher CT(50)/IC(50) ratios than the other isolates. These differences were not related to sensitivity of the corresponding viruses to AZT but to the occurrence of certain mutations in their pol gene. The four deviating isolates contained either a minimum of four AZT-specific substitutions, including Thr-215-->Tyr (isolates 134 and 143), or some of the known specific substitutions combined with Thr-39-->Ala (isolates 80 and 157). The Thr-39-->Ala substitution has previously been recorded in connection with AZT/Foscarnet combination therapy.
 ...
PMID:Application of a colorimetric chain-termination assay for characterization of reverse transcriptase from 3'-azido-2',3'-deoxythymidine-resistant HIV isolates. 1207 93

Phosphonoformate (foscarnet) is a pyrophosphate (PP(i)) analogue and a potent inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), acting through the PP(i) binding site on the enzyme. HIV-1 RT can unblock a chain-terminated DNA primer by phosphorolytic transfer of the terminal residue to an acceptor substrate (PP(i) or a nucleotide such as ATP) which also interacts with the PP(i) binding site. Primer-unblocking activity is increased in mutants of HIV-1 that are resistant to the chain-terminating nucleoside inhibitor 3'-azido-3'-deoxythymidine (AZT). We have compared the primer-unblocking activity for HIV-1 RT containing various foscarnet resistance mutations (K65R, W88G, W88S, E89K, S117T, Q161L, M164I, and the double mutant Q161L/H208Y) alone or in combination with AZT resistance mutations. The level of primer-unblocking activity varied over a 150-fold range for these enzymes and was inversely correlated with foscarnet resistance and directly correlated with AZT resistance. Based on published crystal structures of HIV-1 RT, many of the foscarnet resistance mutations affect residues that do not make direct contact with the catalytic residues of RT, the incoming deoxynucleoside triphosphate (dNTP), or the primer-template. These mutations may confer foscarnet resistance and reduce primer unblocking by indirectly decreasing the binding and retention of foscarnet, PP(i), and ATP. Alternatively, the binding position or orientation of PP(i), ATP, or the primer-template may be changed in the mutant enzyme complex so that molecular interactions required for the unblocking reaction are impaired while dNTP binding and incorporation are not.
 ...
PMID:Relationship between 3'-azido-3'-deoxythymidine resistance and primer unblocking activity in foscarnet-resistant mutants of human immunodeficiency virus type 1 reverse transcriptase. 1274 70

Objective: The Authors report their experience of Cytomegalovirus (CMV) retinitis therapy in HIV patients, using Ganciclovir and Foscarnet in monotherapy. They also evaluate the reliability of the Polymerase Chain Reaction (PCR) through the qualitative technique as an index of active disease. Methods: 18 patients suffering from CMV retinitis were treated: Ganciclovir was administered at a dosage of 10 mg/kg b.w./day and Foscarnet at 180 mg/kg b.w./day, both of them for 21 days during the induction phase. During the mantainance phase the former was administered at 5 mg/kg b.w./day and the latter at 90 mg/kg b.w./day for 5 days a week. Results: Both the drugs induced the stabilization or regression of the lesions. There was however a relapse with both therapies. We did not observe a significant difference either in the entity and the duration of the stabilization or in the survival from diagnosis time. Finally the PCR method was not helpful in the diagnosis of CMV retinitis.
 ...
PMID:[Observations about the treatment of Cytomegalovirus retinitis in patients with HIV infection using Ganciclovir and Foscarnet] 1276 86

A new enzyme-labile group called S-acyl-3-thiopropyl group (SATP) has been synthesized from allylic esters of phosphonate. After demonstration of the enzyme-labile character of the SATP in cellular extracts, it has been introduced onto the phosphonate moiety of PFA (Foscarnet) to obtain potential lipophilic prodrugs. To ponder the lipophilicity of the triesters of PFA, esters of monomethylether of polyethyleneglycols and of thioglycerol were introduced on the PFA carboxylate moiety. The SATP groups were introduced in an attempt to deliver PFA after bioactivation inside the cells. The PFA prodrugs were evaluated in vitro for their activity against human immunodeficiency viruses (HIV-1 and HIV-2).
 ...
PMID:Synthesis and in vitro evaluation of S-acyl-3-thiopropyl prodrugs of Foscarnet. 1501 12

Extracts from twenty two medicinal plants popularly used in preparing traditional remedies in Kenya were screened for activity against the HIV-1 reverse transcriptase. The screening procedure involved the use of tritium labeled thymidine triphosphate as the enzyme substrate and polyadenylic acid.oligodeoxythymidylic acid [poly(rA).p(dT)12-18] as the template primer dimer. Foscarnet was used as a positive control in these experiments. At a concentration of 100 microg/ml, extracts from eight of these plants showed at least 50 per cent reverse transcriptase inhibition. This activity was arbitrarily considered as significant. This indicates that there is the probability that some antiretroviral compounds could be identified and isolated from materials from these plants.
 ...
PMID:Evaluation of the HIV-1 reverse transcriptase inhibitory properties of extracts from some medicinal plants in Kenya. 1729 48

Foscarnet (phosphonoformate trisodium salt), an antiviral used for the treatment of HIV and herpes virus infections, also acts as an activator or inhibitor of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Interaction of the drug with 11 CA isozymes has been investigated kinetically, and the X-ray structure of its adduct with isoform I (hCA I-foscarnet complex) has been resolved. The first CA inhibitor possessing a phosphonate zinc-binding group is thus evidenced, together with the factors governing recognition of such small molecules by a metalloenzyme active site. Foscarnet is also a clear-cut example of modulator of an enzyme activity which can act either as an activator or inhibitor of a CA isozyme.
 ...
PMID:Phosph(on)ate as a zinc-binding group in metalloenzyme inhibitors: X-ray crystal structure of the antiviral drug foscarnet complexed to human carbonic anhydrase I. 1731 45

Foscarnet, licenced by Astra pharmaceutical products, is a pyrophosphate analogue that selectively inhibits replication of viruses in infected cells. It inhibits in vitro the replication of all herpes viruses, including human cytomegalovirus (HCMV) at concentrations of 100 to 300 mumol/l and has a dose-related inhibitory effect on HIV-1 virus, influenza virus and hepatitis B virus. It does not require intra-cellular phosphorylation for antiviral activity. Oral bioavailability of foscarnet is low (12-22%), and foscarnet must be administered intravenously. It is mainly eliminated unchanged by the kidneys. Mean half-life in plasma ranges from 3.4 to 5 h. For acute therapy, the currently recommended regimen is 60 mg/kg t.i.d. or 90-100 mg/kg b.i.d. In AIDS patients, foscarnet is an effective treatment of HCMV retinitis. Healing or stabilisation of lesions is obtained in 85-95% of patients after 2 weeks or 3 weeks therapy. For HCMV gastrointestinal disease, complete or partial response rates of 57-95% have been reported with foscarnet. The optimal maintenance dosage of foscarnet necessary in CMV infections in AIDS patients remains to be clearly established. Data from small samples size studies have shown that foscarnet decreased significantly circulating levels of HIV antigen in AIDS patients with HCMV disease. Foscarnet is an effective treatment for acyclovir-resistant herpes simplex virus and for acyclovir-resistant varicella-zoster virus (40 mg/kg every 8 h). In patients with immunosuppression not HIV-related HCMV infections, particularly interstitial pneumonia in transplant recipients, experience with foscarnet is limited. The major adverse effect of foscarnet is reversible renal dysfunction, due to acute tubular toxicity. In may be partially prevented by hyperhydratation during the treatment. Fluctuations in serum calcium and phosphore levels, with both increase and decrease are also frequent adverse reactions. Most clinical symptoms are related to decrease in ionized calcium levels. Hyperphosphatemia, a clinically benign phenomenom, reflects the incorporation of foscarnet in bone. Penile ulcerations have been described and may result from mococutaneous direct toxicity of foscarnet eliminated in urine. Although relapses frequently occur after a few months of maintenance therapy, foscarnet that shows a marked activity against HCMV in vitro, has allowed important progress in therapy of HCMV infections in AIDS patients.
 ...
PMID:Pharmacology and clinical use of foscarnet. 1861 71


<< Previous 1 2 3 4 Next >>