gem91 and Acquired-Immunodeficiency-Syndrome

The experimentation on human beings of one or several therapeutic molecules discovered in laboratory is necessary and important because it helps to find new treatments or new diagnostic methods. But, it presents serious ethical problems. In this article we are analysing the example of the HIV infection. We are succinctly describing the research methods in laboratory for therapeutic molecules, first the experimentation on animals and then on human being in clinical trials. We will then try to show, with several examples, how during these last 25 years of HIV infection, the research of new molecules has not always respected the ethical rules set out in Helsinki declaration, "Code de la santé publique" or "Guide de bonnes pratiques cliniques-ICH" etc. We are discussing here the way to avoid these irregularities.

Topics: Acquired Immunodeficiency Syndrome; Adenine; Animals; Anti-HIV Agents; Azathioprine; Clinical Trials as Topic; Congresses as Topic; Cyclosporine; Developing Countries; Ditiocarb; Double-Blind Method; Drug Evaluation, Preclinical; Drug Therapy, Combination; Ethics Committees, Research; Human Experimentation; Humans; Informed Consent; Mass Media; Oligodeoxyribonucleotides, Antisense; Organophosphonates; Practice Guidelines as Topic; Stavudine; Tenofovir; Thionucleotides

Inhibition of human immunodeficiency virus (HIV) replication by oligonucleotides is a complex process and may be implemented by an array of antiviral mechanisms. These include inhibition of virus adsorption to the host cell, inhibition of transcription via antisense or as the result of triple helix formation, and inhibition of viral encoded enzymes such as reverse transcriptase and integrase. Since the particular mechanism of HIV inhibition depends on the oligonucleotide (ON) sequence and the ON chemical modifications, the design and synthesis of potent HIV inhibitors has been an important and rewarding focus of ON research. In this era of great concern that HIV may rapidly display resistance to any antiviral compound with one mechanism of viral inhibition, oligonucleotides are potentially attractive alternatives for therapy. Several ONs have entered clinical evaluation in AIDS patients. At present Zintevir, which inhibits both HIV adsorption and HIV integrase, is in phase I/II clinical trials.

Topics: Acquired Immunodeficiency Syndrome; Adsorption; Animals; Anti-HIV Agents; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Drug Design; Drug Evaluation, Preclinical; Gene Expression Regulation, Viral; Genetic Therapy; HIV; HIV Integrase; HIV Integrase Inhibitors; HIV Reverse Transcriptase; Macaca fascicularis; Mice; Mice, SCID; Nucleic Acid Conformation; Oligodeoxyribonucleotides; Oligodeoxyribonucleotides, Antisense; Oligonucleotides; Oligonucleotides, Antisense; Rats; Reverse Transcriptase Inhibitors; RNA, Viral; Thionucleotides; Virus Replication

Topics: Acquired Immunodeficiency Syndrome; Antiviral Agents; Base Sequence; CD4-Positive T-Lymphocytes; Cell Line; Genes, gag; HIV-1; Humans; Molecular Sequence Data; Oligodeoxyribonucleotides, Antisense; Oligonucleotides, Antisense; Thionucleotides; Virus Replication