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)

A table charts the various nomenclature of drugs used to treat HIV and AIDS. The common name, generic name, and brand name are given for several categories including NARTIs (NRTIs, "Nukes", Nucleoside analogue reverse transcriptase inhibitors), NNRTIs (Non-nucleoside reverse transcriptase inhibitors), and PIs (Protease Inhibitors). Other drugs listed are Hydroxyurea (anti-cancer drug) and preveon (Adefovir (Nucleotide)).
 ...
PMID:What's in a name? 1136 57

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.
 ...
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.
 ...
PMID:Adefovir: FDA committee votes against approval. Food and Drug Administration. 1136 70

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.
 ...
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.
 ...
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.
 ...
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.
 ...
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.
 ...
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.
 ...
PMID:Selection of a T-cell line resistant to stavudine and zidovudine by prolonged treatment with stavudine. 1221 22

Because prevention of heterosexual HIV transmission is not always possible, it is important to develop effective strategies of postexposure prophylaxis (PEP). Since in vivo comparison of drug potency is difficult, we developed an in vitro model with cells resembling primary targets during sexual transmission: monocyte-derived dendritic cells (MO-DCs), Langerhans cells (MO-LCs), and resting autologous CD4(+) T cells. Nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs, respectively) were evaluated for their antiviral activity, when added immediately after infection or at a later time point. In parallel, their immune-suppressive effect was examined by measuring inhibition of mixed MO-DC/allogeneic CD4(+) T cell cultures. Most RTIs potently inhibited HIV replication, even if added 24 hr after infection (representing PEP). The sensitivity to antiretroviral drugs was similar in HIV-infected MO-DCs and MO-LCs, but decreased in cocultures with resting autologous CD4(+) T cells. The NNRTIs efavirenz and UC-781 as well as the NRTIs AZT, 3TC, and d4T showed a similar high potency in MO-DC plus autologous CD4(+) T cell cocultures as compared with CEM T cells, whereas their activity in phytohemagglutinin/interleukin 2 (PHA/IL-2)-activated CD4(+) T cells was lower. The dideoxynucleoside RTI abacavir as well as the phosphonates (R)-PMPA and PMEA were more active in infected MO-DCs as compared with either CEM T cells or PHA/IL-2 activated CD4(+) T cells. Infection in cocultures of MO-DCs and autologous CD4(+) T cells could be aborted in a proportion of the cultures, with high concentrations of PMEA and/or efavirenz, but not with AZT. Suppressive activity in mixed leukocyte cultures was observed only at very high concentrations of RTI. Our data suggest that cocultures of MO-DCs and autologous CD4(+) T cells can be used as a possible in vitro model to explore protocols for PEP after sexual HIV transmission.
 ...
PMID:Activity of reverse transcriptase inhibitors in monocyte-derived dendritic cells: a possible in vitro model for postexposure prophylaxis of sexual HIV transmission. 1239 48


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>