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)

Therapeutic intervention with highly active antiretroviral therapy (HAART) can lead to the suppression of HIV viremia below the threshold of detection for several years. However, impact of HAART on reconstitution of virus-specific immune responses remains poorly understood. In this study, four macaques were infected with pathogenic SHIV(KU). One week postinoculation two of the four animals were treated with PMPA [9-R-(2-phosphophomethoxypropyl)adenine] daily for 83 days. Two other macaques, that did not receive treatment, exhibited explosive virus replication accompanied by a near total loss of CD4(+) T cells and succumbed to AIDS-related complications within 6 months of infection. These animals did not develop any virus-specific immune responses. On the contrary, the animals that received PMPA showed transient loss of CD4(+) T cells that recovered during the treatment period. The virus burden declined below the level of detection that rebounded soon after cessation of PMPA therapy. The virus replicated productively for several weeks before both animals controlled the productive replication of virus. This control of virus replication was found to be associated with the development of virus-specific neutralizing antibodies, T-helper cells, and CTLs. Although PMPA did not eliminate virus from the animals, it provided them with enough time to mount virus-specific immune responses that eventually controlled the virus replication in the blood. Our results suggest that antiretroviral therapy, if initiated early during infection, would help the host in mounting virus-specific immune responses that might control productive replication of the virus.
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PMID:Development of virus-specific immune responses in SHIV(KU)-infected macaques treated with PMPA. 1114 93

Virtually all the compounds that are currently used, or under advanced clinical trial, for the treatment of HIV infections, belong to one of the following classes: (i) nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs): i.e. zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir, emtricitabine, tenofovir (PMPA) disoproxil fumarate; (ii) non-nucleoside reverse transcriptase inhibitors (NNRTIs): i.e. nevirapine, delavirdine, efavirenz, emivirine; and (iii) protease inhibitors (PIs): i.e. saquinavir, ritonavir, indinavir, nelfinavir and amprenavir. In addition, various other events in the HIV replicative cycle are potential targets for chemotherapeutic intervention: (i) viral adsorption, through binding to the viral envelope glycoprotein gp120; (ii) viral entry, through blockade of the viral coreceptors CXCR4 and CCR5; (iii) virus-cell fusion; (iv) viral assembly and disassembly; (v) proviral DNA integration; (vi) viral mRNA transcription. Also, new NRTIs, NNRTIs and PIs have been developed that possess respectively improved metabolic characteristics, or increased activity against NNRTI-resistant HIV strains or, as in the case of PIs, a different, non-peptidic scaffold. Given the multitude of molecular targets with which anti-HIV agents can interact, one should be cautious in extrapolating from cell-free enzymatic assays to the mode of action of these agents in intact cells.
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PMID:New developments in anti-HIV chemotherapy. 1134 62

PMPA, an experimental anti-HIV drug, is a member of a new class of drugs called nucleotide analogs. PMPA gained attention when it was reported that it completely protected macaque monkeys from SIV (a virus closely related to HIV). No other potential treatment has been able to do this. It is difficult to tell how quickly nucleotide analogs can work because, for unknown reasons, viral loads show only modest reductions even when other information suggests that they may be working better than the viral loads imply. PMPA is undergoing standard animal toxicology tests in preparation for human trials. The first nucleotide analog likely to reach widespread human use is bis-POM PMEA, since it is already in human trials.
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PMID:PMPA in perspective. 1136 50

The Centers for Disease Control and Prevention (CDC) plans to update its guidelines on management of occupational exposure to HIV and will reopen the issue of using AZT as prophylaxis. Increasing evidence shows that workers occupationally exposed to HIV do not seroconvert when given AZT as prophylaxis. Additionally, animal research has shown PMPA to provide complete prophylaxis against simian immunodeficiency virus in macaque monkeys.
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PMID:CDC to revisit AZT, post-exposure guidelines. Centers for Disease Control and Prevention. 1136 28

Adefovir dipovixil (formerly bis-POM PMEA) is Gilead Science's experimental anti-HIV drug. It has a very long half-life within the body, which means that it only needs to be taken once a day. It shows broad-spectrum antiviral activity against hepatitis B and herpes viruses, especially CMV and Epstein Barr, in addition to its activity against HIV. Adefovir and PMPA, new derivatives now entering clinical trials, are nucleotide analogs, which are similar to nucleoside analogs but do not need to undergo as much processing within cells to become active. Both classes of drugs attack reverse transcriptors, so HIV resistance can cover both drug classes at once. Both drugs reduced viral load by 70 percent at differing levels, but viral load rebounded when treatment was stopped. Side effects occurred more frequently at higher dosages. The fear in using these drugs for HIV treatment is that patients risk developing breakthrough CMV infections which are cross-resistant to adefovir and other CMV medications. It may be best to limit adefovir to those needing it for CMV prophylaxis.
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PMID:And also, "adefovir dipovixil". 1136 85

Recent studies are indicating that the standard version of saquinavir is not an appropriate anti-HIV regimen protease inhibitor for beginning therapy. In addition, the new soft gel capsule formulation of saquinavir shows better activity than the available hard gel formulation (HGC), warranting its classification as a highly active antiviral for patients who have not previously used the HGC. Studies are showing that patients who had previous HGC therapy do not gain significant benefit from the new drug, suggesting that HGC saquinavir should not be used as first-line therapy. Advertising that promoted the improved drug has been withdrawn at the request of Project Inform because of the lack of warning labels necessary due to dosing problems. An indinavir study in Brazil (study had questionable ethics) reveals a dramatic difference in the percentage of people developing AIDS in groups receiving indinavir compared to those receiving AZT alone. Also, small studies of intravenous PMPA are showing that this nucleotide analogue reverse transcriptase inhibitor possesses potent anti-HIV activity. An oral form of PMPA has been developed and is currently undergoing clinical trials. While clinical studies are showing which drugs are most effective, there is still limited practical information on the best uses, causing physicians to experiment with dosages without the benefit of clinical trial information.
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PMID:Update on antivirals. 1136 79

The 5th Conference on Retroviruses and Opportunistic Infections included 837 abstracts and oral presentations on clinical and basic science aspects of HIV. A major theme of the conference was the effectiveness of newer anti-HIV therapies, and there were many sessions dealing with combination treatments, including six-drug treatments. Results of studies with several drugs, including abacavir, efavirenz, amprenavir, PMPA Prodrug, adefovir dipivoxil, hydroxyurea, and protease inhibitors in several combinations are summarized. Treatments for opportunistic infections, including MAC, CMV retinitis, herpesvirus, and tuberculosis, are also presented.
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PMID:Selected highlights from the 5th Conference on Retroviruses and Opportunistic Infections. 1136 69

Reports at the 5th Conference on Retroviruses and Opportunistic Infections addressed new anti-HIV agents in primary phases of development that offer treatment alternatives to people with little or no treatment history and individuals with few treatment choices. FTC, a new nucleoside analog produced by Triangle Pharmaceuticals, is an alternative to 3TC. F-ddA (lodenosine), a nucleoside analog licensed by US Bioscience, is structurally similar to ddI and is reported to have good bioavailability, once-a-day dosing, and no bone marrow suppression. F-ddA has also shown in vitro activity against multidrug-resistant strains of HIV. Adult and pediatric studies are currently being conducted by the National Cancer Institute (NCI) and US Bioscience. Oral versus IV PMPA shows promising results as a possible alternative for 3TC- and AZT-experienced patients. Further testing is being done by Gilead Sciences and HIV Network for Prevention Trials (HIVNET). Abbott Laboratories is developing a second-generation protease inhibitor, ABT-378, which has a ten-fold greater antiviral activity in vitro than the original, ritonavir. It is administered with ritonavir to increase ABT-378 levels in the blood, but has no food requirements, and less severe side effects. Two trials are being conducted: one for patients who are treatment-naive and the second for patients who are failing other protease inhibitors. Immune-based therapies, such as Leukine (GM-CSF), are used to handle neutropenia and offset bone marrow toxicities from drugs. Concerns that GM-CSF may increase viral replication may be balanced by using highly active antiretroviral therapy. FP-21399, developed by Lexigen Pharmaceuticals, is being tested as an HIV fusion inhibitor.
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PMID:Looking down the drug pipeline. 1136 93

Since many new anti-HIV drugs are variations of currently available drugs, they may be more effective for people who are beginning treatment. One study shows favorable results when using efavirenz in triple combination therapy; however, it is recommended that this therapy be reserved for people who are treatment-naive and symptom-free. It is still unclear if all non-nucleoside RT inhibitors (NNRTIs) are as potent as efavirenz and whether the long-term potential for them is as promising as standard combinations. Researchers caution against pairing an NNRTI with a protease inhibitor in the event that resistance to the combination develops. That resistance may eliminate the option of using any other protease inhibitor or NNRTI in future therapies. Conversely, abacavir, an NARTI, has been effective in combination with many protease inhibitors. Amprenavir shows good antiviral activity; although studies show that it may not be successful as a salvage therapy with protease inhibitors. Nucleotide analogue reverse transcriptase inhibitors, such as adefovir and bis-poc PMPA, showed moderate anti-HIV potency. A study evaluating FTC alone showed a good reduction in viral load. FTC also fights hepatitis B and requires only one dose daily. Information is included about expanded access programs for abacavir, adefovir, and efavirenz.
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PMID:New drugs on the horizon. 1136 12

Three experimental drugs, ABT-378, PMPA, and T-20, are now or soon will be available through limited early access programs. The protease inhibitor ABT-378, developed by Abbott Laboratories, is able to suppress many viral mutations which are resistant to other protease inhibitors. For patients with many failed regimens, ABT-378 combined with other new drugs, such as PMPA or T-20, may be the most successful treatment. PMPA, developed by Gilead Sciences, is in the same class as adefovir; however, PMPA, now called tenofovir, seems to be both safer and more active against HIV. T-20, the first of the fusion inhibitor class, works by preventing HIV from attaching itself to and entering a cell. No cross resistance between T-20 and other antiretroviral drugs is expected.
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PMID:ICAAC: new drugs in late breaker session. 1136 17


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