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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many of the presentations at the 5th Conference on Retroviruses and Opportunistic Infections were prompted by great successes in treating HIV. There are now more than 300 possible drug combinations, and many promising drugs are under development. Results of tests of several drugs, individually and in combination, are presented. Nucleoside analogs, generally in triple combinations, were well tolerated and led to undetectable viral loads. Crixivan is as effective in twice-daily doses as it is in the FDA-mandated three-times-a-day regimen. People with advanced HIV did better when they started with triple combinations with Crixivan, than those with advanced HIV who started on dual therapy or monotherapy. Viracept treatment resulted in undetectable viral loads in up to 92 percent of the participants in a study group. There are several studies underway to test the safety and effectiveness of combinations that include two protease inhibitors. Two experimental drugs, FTC and hydroxyurea (HU), were noted as having strong potential for HIV treatment.
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PMID:Update from the 5th Conference on Retroviruses and Opportunistic Infections. 1136 83

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

Several new antiretroviral agents were discussed at the 6th Conference on Retroviruses and Opportunistic Infections. Some of the new agents described were nucleoside analog reverse transcriptase inhibitors (NRTIs), such as FTC and lodenosine (FddA). Non-nucleoside reverse transcriptase inhibitors (NNRTIs) were also presented and include AG 1549 (formerly S 1153) and DPC 961. In addition, some protease inhibitors (PIs) were mentioned. These PIs include ABT-378/r and AG 1776. A new fusion inhibitor, called T-20 (Trimeris), was also discussed.
Hopkins HIV Rep 1999 Mar
PMID:New antiretroviral agents. 1136 48

A brief review is provided for several oral presentations on HIV drugs delivered at the 6th Conference on Retroviruses and Opportunistic Infections. Topics cover cross resistance with respect to potential new drugs, the new protease inhibitor ABT-378, Triangle Pharmaceuticals' drug FTC, and one study on the different classes of anti-HIV drugs now on the market. Viral load reduction data are highlighted for Zerit/Videx when combined with 3TC, Viramune, or Indinavir. Contact information is provided.
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PMID:The latest antiviral news. 1136 51

Highlights from the 38th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) included a tribute to Jonathan Mann and Mary-Lou Clements Mann and a review of HIV drugs recently approved and currently in development. Information is provided about efavirenz, abacavir, amprenavir, and adefovir, including the classification, dosing, and side effects of these drugs. Data from recent trials of these new drugs can be used to determine the best course of treatment for treatment-naive and treatment-experienced patients. New nucleoside reverse transcriptase inhibitors reviewed are lodenosine (FDDA), FTC, BCH-10652, and DAPD. Non-nucleoside reverse transcriptase inhibitors described include MKC 442 and PNU 142721. Other drugs under development include bis(POC) PMPA, a nucleotide RTI, and several protease inhibitors. T-20, an enzyme that interferes with envelope fusion, is also in development.
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PMID:Antiretroviral update from the Interscience Conference on Antimicrobial Agents and Chemotherapy. 1136 83

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

Despite of 18 licensed antiretroviral drugs in Germany, there is an increased pressure for development of new substances and new targets in the treatment of HIV positive patients. Multidrug resistance and poor pharmacokinetics are the biggest problems we have to fight with. But there is hope for resolving these challenges. Second generation drugs like FTC and DPC 083 with once a day dosage and a high resistance barrier are tested in clinical trials. In addition new classes of HIV drugs are available in phase III trials (T-20 fusion inhibitor). So the future will provide us with some new effective arms in the battle against HIV.
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PMID:[New antiretroviral drugs. Improved pharmacokinetics and simpler dose schedules]. 1137 68

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 (AZT), didanosine (ddI), zalcitabine (ddC), stavudine (d4T), lamivudine (3TC), abacavir (ABC), emtricitabine [(-)FTC], tenofovir (PMPA) disoproxil fumarate; (ii) non-nucleoside reverse transcriptase inhibitors (NNRTIs): i.e., nevirapine, delavirdine, efavirenz, emivirine (MKC-442); and (iii) protease inhibitors (PIs): i.e., saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, and lopinavir. In addition to the reverse transcriptase and protease step, 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 (polysulfates, polysulfonates, polyoxometalates, zintevir, negatively charged albumins, cosalane analogues); (ii) viral entry, through blockade of the viral coreceptors CXCR4 and CCR5 [bicyclams (i.e. AMD3100), polyphemusins (T22), TAK-779, MIP-1 alpha LD78 beta isoform]; (iii) virus-cell fusion, through binding to the viral glycoprotein gp41 [T-20 (DP-178), T-1249 (DP-107), siamycins, betulinic acid derivatives]; (iv) viral assembly and disassembly, through NCp7 zinc finger-targeted agents [2,2'-dithiobisbenzamides (DIBAs), azadicarbonamide (ADA) and NCp7 peptide mimics]; (v) proviral DNA integration, through integrase inhibitors such as L-chicoric acid and diketo acids (i.e. L-731,988); (vi) viral mRNA transcription, through inhibitors of the transcription (transactivation) process (fluoroquinolone K-12, Streptomyces product EM2487, temacrazine, CGP64222). Also, in recent years new NRTIs, NNRTIs and PIs have been developed that possess respectively improved metabolic characteristics (i.e. phosphoramidate and cyclosaligenyl pronucleotides of d4T), or increased activity against NNRTI-resistant HIV strains [second generation NNRTIs, such as capravirine and the novel quinoxaline, quinazolinone, phenylethylthiazolylthiourea (PETT) and emivirine (MKC-442) analogues], or, as in the case of PIs, a different, non-peptidic scaffold [i.e. cyclic urea (DMP 450), 4-hydroxy-2-pyrone (tipranavir)]. 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. A number of compounds (i.e. zintevir and L-chicoric acid, on the one hand; and CGP64222 on the other hand) have recently been found to interact with virus-cell binding and viral entry in contrast to their proposed modes of action targeted at the integrase and transactivation process, respectively.
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PMID:New developments in anti-HIV chemotherapy. 1156 82

Computer modeling studies have been performed on the several pairs of D- and L-nucleoside inhibitors with the HIV-1 RT model. Additionally, clinically important M184V mutation, which confers the viral resistance against 3TC and FTC, were studied by the same modeling system.
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PMID:Understanding the mode of action of L-nucleosides as antiviral agents: a molecular modeling approach. 1156 52

Triangle Pharmaceuticals is developing DAPD, a prodrug of the viral replication inhibitor dioxolane guanosine, as a potential therapy for HIV and HBV infection. Phase I/II dose range studies have commenced for HIV, and clinical development for HBV was to have commenced by late 1999 [319145], [319956]. Phase II trials are scheduled for the second quarter of 2001. The FDA has designated DAPD as a Fast Track product [365894]. DAPD is from a different nucleoside series to FTC and CS-92, which are also in development by Triangle. The compound may offer advantages over several nucleosides from other series that are already on the market because of its unique structure and pharmacological properties [247083]. Both DAPD and DXG are dioxolane purine nucleoside analogs [319660]. Preclinical data suggest DAPD may be of use in combination therapies for HIV-infected patients who are therapy-naive, in addition to patients who have previously received treatment and including those infected with drug-resistant strains of HIV-1 [341145], [341335]. Triangle licensed DAPD from Emory University [216900]. In June 1999, Triangle and Abbott Laboratories entered into an alliance for the development and marketing of six antiviral products, including DAPD [326824].
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PMID:DAPD (Emory University/Triangle Pharmaceuticals/Abbott Laboratories). 1157 3


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