Immunostimulators

During 20 years different oral immunostimulators have been developed and tested in the National Center of Infectious and Parasitic Diseases in Sofia, Bulgaria. Some of them are widely and quite successfully used in clinical practice for immunotherapy and immunoprophxis (Respivax, Urostim, Dentavax). Data on the immunostimulating activity of polybacterial immunostimulants are presented. Numerous clinical investigations, including double-blind studies, have convincingly demonstrated their high efficacy in the prevention and treatment of non-specific infections of the respiratory organs, the urogenital tract, the oral mucosa and periodontium, as well as in the complex therapy of AIDS. All these facts suggest that immunostimulators, in particular polybacterial ones, are a highly promising tool of modern immunotherapy and immunoprophylaxis aimed at the beneficial modulation of immune response in humans.

Most initial work with HIV vaccines was directed at developing vaccines that elicited neutralizing antibodies. These neutralizing antibodies have been narrow in the focus of their action and specific almost entirely to the strain of the innoculating virus. Additionally, controversy has been reported about both the design of assay systems to measure the neutralization of such isolates and interpretation of the results. Researchers are now looking for a "broad-spectrum" vaccine; however, the high variability of the HIV envelope glycoprotein and its rapid rate of mutation creates an elusive target. Safety concerns have reduced interest in live attenuated virus or whole killed virus vaccines. Some novel approaches being taken include increasing cytotoxic T-lymphocyte responses, induction of immune responses in mucosal tissue surfaces, peptide-based vaccines, oligomeric envelope protein-based vaccine regimens, recombinant Tat protein vaccines, natural killer T-cell (NKT) ligand serving as adjuvant, and fusion of SIV gag with the extracellular domain of CTLA-4 as adjuvant. Most of the HIV vaccines currently in development are the products of recombinant DNA technology.

Neurol Clin. 2002 Nov;20(4):983-1011.
HIV-1 infection and AIDS.
Belman AL.
Departments of Neurology and Pediatrics, HSC T 12-020, School of Medicine, State University of New York at Stony Brook, Stony Brook, NY 11794-8121, USA.

Since the initial descriptions of AIDS in the late 1970s, much has been learned about the biology of HIV-1 and the cells it infects. Much has also been learned about mother-to-infant viral transmission and the natural history of HIV-1 infection. Key studies led to strategies for interrupting mother-to-infant transmission, resulting in a significant decline in neonatal HIV-1 infection. More proficient diagnostic techniques made early diagnosis of HIV-1-infected neonates and infants possible during asymptomatic or mildly symptomatic disease stages. Major advances in treatment led to the control of viral replication and thereby altered the course of disease progression. HIV-1/AIDS-associated neurologic disorders declined in parallel. In countries where these therapies are readily available, a dramatic decline in the number of infants born HIV-1 infected has been realized as has a markedly improved survival rate of those infected. Many questions remain, however. The long-term effects of prenatal exposure to antiretroviral agents are not yet known and continue to be studied. Just exactly how HAART therapy may affect early signs of pediatric HIV-1/AIDS-associated CNS disease, should they develop, is unclear. As new anti-retroviral agents are developed and new combination drug regimens are instituted, the potential for neurologic complications, toxicities, and adverse drug interactions (e.g., with antiepileptic drugs (AEDS)) exists and needs to be identified and monitored.

PIP: A 15-member medical research team at Tygerberg Hospital in Cape Town, South Africa, has developed a compound which halted, and even reversed, the progression of HIV disease in human clinical trial subjects. The compound is a mixture of sterols and sterolins, which are found in all plants, yet identified through the more than $10 million of medical research and clinical trial funding provided by Essential Sterolin Products, a small, family-owned South African pharmaceutical company which has recently acquired a world patent for the compound. The compound does not affect viral replication, but instead helps the patient's natural immune system fight off HIV. 300 volunteers with HIV were involved in the double-blind placebo clinical trials launched in 1993. The compound's therapeutic power became clear after 6 months, so the trial was ended on ethical grounds. Administration of the compound has halted patients' physical deterioration, T-cell counts have increased by several hundred percent in some patients, HIV loads are decreasing, there have been no apparent side effects, and patients report both weight gain and a reduction in skin irritations. The compound is taken in pill form three times per day before meals at the current cost of approximately 40 US cents per day. The head of Essential Sterolin Products wants to keep the compound's price low so that people with HIV can afford it. The company is currently negotiating with two international drug corporations to market the compound worldwide as therapy for HIV patients. The capsules are already on the market in South Africa as a food supplement in health nutrition stores.