CMEonHIV.com is dedicated to providing online CME presentations (slides with voiceover) on HIV/AIDS for healthcare professionals given by local and international experts to keep you up-to-date on the ongoing developments in the field.
Conference
"Post 10th Conference on Retroviruses and Opportunistic Infections" Dr. Marina Klein (biography) English - 2003-03-11 - 42 minutes
(44 slides)
Summary : Dr Marina B. Klein presents here the salient features of selected topics from the 10th CROI which took place in Boston in February 2003. New epidemiological data reflect the importance of initiation of antiretroviral therapy (ARV) when the CD4 cell count is still above 350 (Poster 910) even with durable virologic control (Poster 570), to get the most favourable outcomes in terms of clinical manifestations and mortality. An update follows on the treatments for Hepatitis C and HIV/HCV coinfection : comparisons of peg-IFNa2b/Ribavirin versus IFNa/Ribavirin (abstracts 841, 842) and associated toxicities (abstract 843); and mitochondrial toxicity with RBV/ddI compared to RBV with other NRTIs (Poster 763). We now also have some preliminary data on the success rate of liver transplantation in HIV and/or HCV coinfected patients (Abstract 155). New studies on ''old drugs'' show comparisons between nevirapine and efavirenz with a backbone therapy of d4T/3TC (2NN Study) talking about treatment success, virologic failure, change in treatment, disease progression and adverse events (oral session 176). The Gilead-903 Trial shows new data on tenofovir in treatment naīve patients, substituting d4T for tenofovir in a triple combination regimen, with a backbone of efavirenz and 3TC (Poster 564b). The presentation closes with a review of new targets, strategies and drugs, touching on RNA interference, fusion inhibitors and the TORO Phase III Trials (abstract 568), pegylated interferon alpha 2b, STIs (HIV NAT Study, abstract 64), Ritonavir boosted Tipranavir - a non-peptidic PI (abstract 179), and finally some preliminary data on new therapeutic vaccines (MVA-BN-Nef, ALVAC-HIV 1433(canary pox vaccine), ALVAC-HIV 1433+Lipo-6T combined with IL-2).
Learning objectives : - Review new epidemiological data on HIV/AIDS
- Hepatitis C and HIV/HCV coinfection
- New studies on " old " drugs: nevirapine, efavirenz, d4T and 3TC (2NN Study), and D4T, tenofovirDF, 3TC, EFV(Gilead 903 Study)
New targets, strategies and treatments: RNAi, Fusion inhibitors (T-20, T-1249), the TORO (T-20 vs Optimized Regimen Only) Phase III Trials, peg-IFNa2b, , STIs (HIV NAT Trial), TPVr, and therapeutic vaccines (MVA-BN-Nef, ALVAC-HIV 1433(canary pox vaccine), ALVAC-HIV 1433+Lipo-6T combined with IL-2)
Bibliographic references : Double-stranded nef RNA interferes with human immunodeficiency virus type 1 replication.
Yamamoto T, Omoto S, Mizuguchi M, Mizukami H, Okuyama H, Okada N, Saksena NK, Brisibe EA, Otake K, Fuji YR.
Division of Nutritional Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Aichi 467-8603, Japan.
RNA interference (RNAi) has been reported to be post-transcriptional gene silencing (PTGS) by approximately 500 nucleotide-(nt)-long double-stranded (ds) RNA that specifically targets homologous sequences of messenger RNA. In this report, we describe inhibition of HIV-1 transcription by synthetic dsRNAs constructed with mutated nef genes (nef dsRNAs) derived from long-term non-progressors (LTNPs) using cotransfection of the target gene-expressing plasmid and dsRNA. The effects of nef dsRNAs were examined with luciferase (Luc) reporter which is combined with the HIV-1 (SF2) LTR in persistently HIV-1-infected T cell and macrophage cell lines. At 48 hr, a defective nef dsRNA (556 nt) suppressed Luc activity more potently than did SF2 full-length nef dsRNA (744 nt), suggesting that approximately 500 nt-long nef dsRNA could interfere with the HIV-1 transcription.
Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium. erik.declercq@rega.kuleuven.ac.be
Virtually all the compounds that are currently used or are subject of advanced clinical trials for the treatment of HIV infections, belong to one of the following classes: (i) nucleoside reverse transcriptase inhibitors (NRTIs): i.e., zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir, emtricitabine and nucleotide reverse transcriptase inhibitors (NtRTIs) (i.e., tenofovir 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, amprenavir, and lopinavir. In addition to the reverse transcriptase and protease reaction, various other events in the HIV replicative cycle can be considered as potential targets for chemotherapeutic intervention: (i) viral adsorption, through binding to the viral envelope glycoprotein gp120 (polysulfates, polysulfonates, polycarboxylates, polyoxometalates, polynucleotides, and negatively charged albumins); (ii) viral entry, through blockade of the viral coreceptors CXCR4 (i.e., bicyclam (AMD3100) derivatives) and CCR5 (i.e., TAK-779 derivatives); (iii) virus-cell fusion, through binding to the viral envelope glycoprotein gp41 (T-20, T-1249); (iv) viral assembly and disassembly, through NCp7 zinc finger-targeted agents [2,2'-dithiobisbenzamides (DIBAs), azadicarbonamide (ADA)]; (v) proviral DNA integration, through integrase inhibitors such as 4-aryl-2,4-dioxobutanoic acid derivatives; (vi) viral mRNA transcription, through inhibitors of the transcription (transactivation) process (flavopiridol, fluoroquinolones). Also, various new NRTIs, NNRTIs, and PIs have been developed that possess, respectively: (i) improved metabolic characteristics (i.e., phosphoramidate and cyclosaligenyl pronucleotides by-passing the first phosphorylation step of the NRTIs), (ii) increased activity ["second" or "third" generation NNRTIs ( i.e., TMC-125, DPC-083)] against those HIV strains that are resistant to the "first" generation NNRTIs, or (iii), as in the case of PIs, a different, modified peptidic (i.e., azapeptidic (atazanavir)) or non-peptidic scaffold (i.e., cyclic urea (mozenavir), 4-hydroxy-2-pyrone (tipranavir)). Non-peptidic PIs may be expected to inhibit HIV mutant strains that have become resistant to peptidomimetic PIs. Copyright 2002 Wiley Periodicals, Inc.
USER ACKNOWLEDGES AND AGREES THAT ALL DECISIONS MADE WITH THE ASSISTANCE OR USE OF THE SOFTWARE AND/OR THE WEBSITE AND/OR BASED ON CONTENT FOUND HEREIN WILL BE EXCLUSIVELY THE RESPONSIBILITY OF THE USER.
