[Physiopathologic bases of anti-HIV therapy]

HIV human infections therapy requires at least two different approaches: antiretroviral therapy, and immune system modulation (stimulation or suppression depending on the clinical and biological stage, and upon the pathogenesis of the disease). Because no animal model is today available, little is known about the pathogenic mechanisms of HIV infections in humans. Therefore, only antiviral drugs might be involved in standardized middle or short term clinical trials, because virologic parameters are easily measurable, thought immunomodulators may require more than two or three years before getting informations on their efficiency. AZT is of benefit for treated patients within the first 6 or 8 months of therapy, and, after one year, survival of treated patients seems to be identical to survival of control groups. This might be related to the pharmacokinetic of the drug, which has to be phosphorylated before being active on HIV, and all the susceptible cells to HIV are not able to perform this phosphorylation (macrophages for example). Other therapeutic agents are today either in the early in vitro development (antisens, glycosylation inhibitors), or in phase II clinical trial, and when administered to patients, they do not exhibit any antiviral effect (soluble CD4), suggesting that new pharmacologic administration forms are required.