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

Attendees at the Second International Workshop on Salvage Therapy heard little to make them optimistic about the immediate future of salvage therapy. Treatment veterans with only a few virologic failures stand a slim chance of ongoing viral control. Current salvage treatment, even combination therapy, only pushes viral loads to below 500 copies in 20 to 40 percent of patients, and those patients who have had viral loads suppressed to below 20 copies/mL stand the best chance of having a sustained response to the treatment. Results of several studies are reviewed. Adefovir, which had been considered an option, has performed poorly in trials. One table shows the effects of nonnucleoside reverse transcriptase inhibitor/protease inhibitor (NNRTI/PI) salvage therapy in the NNRTI-naive patient. Another table presents figures to show that salvage success correlates significantly with lower viral loads prior to treatment. A third table shows the "megasalvage" track record, while a fourth presents a proposal for a rapid-assessment salvage study. The concept of using drug holidays as a means to force the immune system to begin fighting HIV on its own remains controversial.
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PMID:Salvage solitaire (or, HAART takes a holiday). 1136 32

The FDA's Antiviral Drugs Advisory Committee voted against approval of adefovir dipivoxil (Preveon) for treating HIV. Although adefovir seems to have modest antiretroviral benefit, there is a risk of serious kidney toxicity in long-term use. Adefovir appears to be far more active in treating hepatitis B than HIV.
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PMID:Adefovir: FDA committee votes against approval. Food and Drug Administration. 1136 70

A Food and Drug Administration (FDA) advisory panel recommended against accelerated approval for adefovir dipivoxil (Preveon). The drug belongs to a new class of drugs, nucleotide reverse transcriptase inhibitors, and was developed by Gilead Sciences as a salvage treatment for people who do not experience adequate viral suppression under other therapies. The unexpected denial was due to safety concerns; in a pivotal study, several patients who took adefovir experienced kidney failure and had to be treated with dialysis. The ramifications of the FDA's decision are not known. About 9,000 people have taken the drug through expanded access programs, and adefovir has also displayed antiviral activity against hepatitis B infections. Gilead is developing another drug, tenofovir DF, which appears more effective against HIV, with fewer side effects.
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PMID:FDA panel fails to recommend adefovir approval. Food and Drug Administration. 1136 49

Updates are provided for new anti-HIV drugs currently in development. ABT-378, Tipranavir, and DMP-450 are among the new protease inhibitors discussed. Drugs from other classes that are discussed include emivirine (Coactinon, formerly MKC-442), FTC (emtricitabine, Coviracil), adefovir (Preveon), and pentafuside (T-20). A small study has found that women using Ritonavir (Norvir) may be at a greater risk for anemia (a decrease in red blood cells), caused by excessive menstrual bleeding or hypermenorrhea. New formulations of Ritonavir and ddI (Didanosine, Videx) are described.
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PMID:New anti-HIV drugs in development. 1136 65

Presentations at the Fifth Conference on Retroviruses and Opportunistic Infections focused on new and novel HIV treatments. Four new agents in advanced testing are described: abacavir (1592), efavirenz (DMP-266), adefovir dipivoxil (bis-POM PMEA), and amprenavir (141W94). Other new drugs are being developed; however, the drugs are not as far along in the testing and approval process. The new drugs include integrase inhibitors, zinc finger inhibitors, cyclams and bycyclams, fusion inhibitors, and CKR-5 gene therapy. A summary of each drug is provided.
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PMID:Novel approaches for the treatment of HIV. 1136 50

Monocyte-derived macrophages (MDMs) play a central role in the pathogenesis of infection by human immunodeficiency virus (HIV-1) and represent one of the main reservoirs of the virus in the body. In addition, MDMs can easily be infected by various herpes viruses, including herpes simplex virus type 1 (HSV-1). We have synthesized a new antiviral agent (Bis-PMEA) that consists of two 9-(2-phosphonylmethoxyethyl)adenine (PMEA) molecules bound by a phosphate bridge. This nucleotide analogue, like the parent compound PMEA, has strong and selective activity against HIV-1 and HSV-1. A drug-targeting system previously developed in our laboratory was used for the selective delivery of these drugs to macrophages. Bis-PMEA and PMEA were encapsulated into autologous erythrocytes by a procedure of hypotonic dialysis and isotonic resealing. Loaded erythrocytes were modified to increase their recognition and phagocytosis by human macrophages. By administering Bis-PMEA-loaded erythrocytes to macrophages, 47% of Bis-PMEA and 28% of PMEA was still present 10 days after phagocytosis; in contrast, only 12% of PMEA was found in macrophages receiving PMEA-loaded erythrocytes. Bis-PMEA-loaded erythrocytes were then added to macrophages infected with HIV-1 and HSV-1 and their antiviral activity evaluated. Remarkable protection was obtained against HIV-1 and HSV-1 infection (95 and 85%, respectively). Therefore, Bis-PMEA acts as an efficient antiviral prodrug that, following selective targeting to macrophages by means of loaded erythrocytes, can protect a refractory cell compartment.
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PMID:Erythrocyte-mediated delivery of a new homodinucleotide active against human immunodeficiency virus and herpes simplex virus. 1138 14

New antiretroviral drugs with activity against strains of human immunodeficiency virus type 1 (HIV-1) with non-B subtypes and with resistance to current antiretroviral drugs are needed. The activity of two nucleotide analogs, tenofovir and adefovir (PMPA and PMEA, respectively), against non-B subtypes and nucleoside-resistant primary HIV-1 isolates was assessed. Tenofovir and adefovir were fully active against a panel of subtypes A, C, D, E, F, G, and group O primary HIV-1 isolates as compared with their respective activity against subtype B isolates. Moreover, the susceptibility of a panel of 10 primary HIV-1 isolates with >10-fold mean resistance to zidovudine, lamivudine, and abacavir was within 2.2-fold of wild-type tenofovir susceptibility for each isolate. An oral prodrug of tenofovir, tenofovir disoproxil fumarate (DF), is currently in phase III clinical trials for the treatment of HIV-1 infection. These in vitro susceptibility results suggest that tenofovir DF may be active in vivo against HIV-1 with nucleoside resistance as well as against HIV-1 with non-B subtypes.
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PMID:Tenofovir, adefovir, and zidovudine susceptibilities of primary human immunodeficiency virus type 1 isolates with non-B subtypes or nucleoside resistance. 1152 86

An antisense oligodeoxynucleotide against the human immunodeficiency virus type 1 (HIV-1) Rev response element, a ribozyme complementary to the HIV-1 5'-LTR, and the reverse transcriptase inhibitors 9-(2-phosphonylmethoxyethyl) adenine (PMEA) and (R)-9-(2-phosphonylmethoxypropyl)-adenine (PMPA) inhibited virus replication in monocyte-derived macrophages more effectively when delivered in pH-sensitive liposomes compared to the free drugs.
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PMID:Enhanced inhibition of HIV-1 replication in macrophages by antisense oligonucleotides, ribozymes and acyclic nucleoside phosphonate analogs delivered in pH-sensitive liposomes. 1156 68

Novel 2-amino-6-arylthio-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) esters were synthesized and evaluated for antihepatitis B virus (HBV) activity in vitro using HB611, HuH-6 cell line, stably transfected with the HBV genome. Among the compounds synthesized, 2-amino-6-phenylthio-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester (8), 2-amino-6-(4-methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester (16), 2-amino-6-(3-methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester (17), and 2-amino-6-(2-methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester (18) showed considerably high anti-HBV activity, as represented by IC(50) values of 0.05, 0.03, 0.04, and 0.08 microM, respectively, and exhibited low cytotoxicity, as represented by CC(50) values of more than 1000 microM. It was suggested that these compounds did not have anti-HIV activity, and compound 8 showed only weak anti-HSV-1 activity. An antiviral agent, 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA), which was used as a control in the present study, showed moderate anti-HBV activity, as represented by an IC(50) value of 0.2 microM. Furthermore, compound 16 was administered orally to mice at a dose of 100 mg/kg in order to examine its gastrointestinal absorbability. Consequently, the main active metabolite was observed in mouse plasma, with especially high concentrations in the liver.
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PMID:2-Amino-6-arylthio-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) esters as novel HBV-specific antiviral reagents. 1208 99

It has been demonstrated that prolonged treatment with nucleoside analogues, such as 3'-azido-3'-deoxythymidine (zidovudine), 2',3'-dideoxycytidine (zalcitabine) and 9-(2-phosphonylmethoxyethyl) adenine (PMEA), may cause selection of cells that are resistant to their anti-HIV activity. A human T-lymphoblastoid cell line that is resistant to the antiviral and cytotoxic activity of 2',3'-didehydro-3'-deoxythymidine (stavudine) has developed as a result of prolonged treatment. These cells, called CEMstavudine, are also less sensitive to zidovudine. The cellular/pharmacological resistance acquired by the CEMstavudine cells is relatively low and appears to correlate with a reduction in thymidine kinase (TK) activity, rather than with a decreased expression of TK mRNA.
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PMID:Selection of a T-cell line resistant to stavudine and zidovudine by prolonged treatment with stavudine. 1221 22


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