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The stakes are big for those among the researchers who will discover a real treatment or vaccine. Now there is the multi-therapy treatment that is excessively constraining. AIDS is difficult to fight back because the viruses can mutate and escape the immune system of the host. In order to model HIV, scientists have tried to infect chimpanzees for 15 years and it took that time to realize that they do not develop the disease as humans do.
AIDS/HIV studies that were based on experimentation on apes are one of the greatest flops that the biomedical community can boast and despite intense research on non-human primates, vaccines will not be available any time soon. There has been a cohort of studies showing that some drug treatments for HIV infection resulted in a marked reduction in morbidity and prolongation of life; this achievement was possible thanks to human studies. However, they are often associated with side effects such as acute and chronic toxicities and the development of resistant viruses limits their effectiveness. Another problem is the cost: they are too expensive and difficult to administer in most third world countries. Then, HIV vaccines have been tested due to their potential to overcome these problems. So far, the most promising findings have shown that an immune response can be stimulated and correlate with a reduced activity of HIV in man. Cytotoxic T-cell responses are important cells of the immune system that promoted a reduced HIV (man) or SIV (simian) viral load and increased CD4 counts in non-human primates or man.
The Division of Microbiology and Immunology of the Yerkes Regional Primate Research Center (Emory University School of Medicine - Atlanta, Georgia, USA) like to study apes but more importantly, they like the fatty NIH grants that enable the researchers to experiment on them. Among the tens of chimpanzees manipulated there, one chimpanzee "C499" was eventually killed in 1996 as a result of a unique development of AIDS in this species, approximately 11 years after infection with HIV-1. Despite the rarity of AIDS in apes, the authors decided to pursue the studies and sampled the blood of C499 and used it to infect other healthy chimpanzees, which resulted in a loss of their CD4 cells. Then, in vitro, they isolated some strains of viruses, from the transfused animals, that resisted to antibody neutralization derived from the serum of C499, whereas the parental viruses used to inoculate C499 were susceptible to neutralization by serum from that animal. In short, it means that the virus that initially infected C499, mutated, developed another phenotype and escaped the immune system of the host. (1) We know that this is through a similar escape mechanism that the human immunodeficiency virus type 1 (HIV-1) enables the AIDS pandemic. As judged by the development of resistant viruses that limit the effectiveness of present vaccines in the patients, and based on epidemiological studies, infecting healthy chimpanzees is both unethical and needless.
Chimpanzees are not the only animals to suffer unnecessarily. Rhesus macaques receive intramuscular injections of viral proteins to elicit an immune response and then are infected with strains of simian or simian-human hybrid virus called SHIV. The rationale behind this type of experiments is based on the assumption that the SIV is a model for HIV, which obviously is not as we note: first, a genetic difference between the viruses, second, the inconsistent findings and variations between strains used for infection and third, the fact that SIV is further recognized to have contributed little to our understanding of the HIV. If a vaccine has a chance to go to clinical trials, the minimum requirement for candidate HIV vaccines is an induced immune response in non-human primates, which means the induction of antibodies neutralizing primary HIV variants or T cell-mediated immune responses. Once a clinical trail is launched, such as the test of vaccines that took place in Oxford and Nairobi, (see Hanke & McMichael, Nature Medicine 6, 951-955, 2000) one would expect that enough animal studies have been done. However, the reader might be surprised to know that it is not the case since sometimes researchers need to show that the vaccines tested in humans, induce the same immune responses in other primates such as rhesus macaques. Why? Allegedly, they need to prove in animals what has been done and demonstrated in humans to augment their confidence that the treatments work in another species. Since studies in humans permitted to obtain important information relative to the human immune system response, and a fortiori, if the vaccines were safe and at some extent efficacious, then why retest the same vaccines in these animals over again? Is it to find an inferior animal model?
When Jane Goodall visited an American laboratory under contract with the NIH, which conducted studies on hepatitis using chimps as recipient of the virus, in 1987, she reported her feelings in a paper where she described the state of depression and despair of the chimps. Young chimps were crammed in tiny cages measuring 22 inches by 22 inches and only 24 inches high. "They could hardly turn . I shall be haunted forever."(2) Now, many of those retired chimps, who were subjected to HIV/hepatitis infections in the USA, live in total isolation. Lonely in dark sheds, they wait until death will relieve them. Until then, no social contacts with other beings are permitted. Although, they had not developed any disease, they are still considered a potential threat. Researchers had some mercy on them and preferred not to put the chimps out of their miserable condition. Those remarkable and endangered creatures are the forgotten legacy of today's scientific brutality.
Now, some scientists are trying to infect monkeys with their own viruses called SIV or hybrid viruses called HSIV. If you listen to the comments of those who study these models they will tell how it was valuable to work on chimps and how valuable it will be to work on monkeys and that they need more primates to experiment on (which implies more money from tax-payers). Viruses are very specific to the host like the HIV. There are still no cure for AIDS and it seems that there is little room in the field for those who come with different ideas or theories on the topic. Zidovudine as anti-cancer drugs has been established in 1985 from in vitro studies, the anti-retroviral multi-therapy has been developed also through in vitro studies and clinical research. AIDS was such a serious pandemic that drugs such AZT bypassed animal tests. Other in vitro studies have helped identify different strains of the virus with different mode of infection through the CD8 receptor. Epidemiological studies have showed the transmission routes of the virus, and electron microscopy has allowed the structural identification of the virus in the human tissue, genetic studies in combination with epidemiological studies have revealed several versions of the viral DNA (polymorphisms).
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1. Juompan L. et al. "Resistance to neutralizing antibody and expanded coreceptor usage are associated with human immunodeficiency virus type 1 isolates derived from chimpanzees with pathogenic infections." AIDS Res Hum Retroviruses 2001 Dec 10; 17(18):1705-14
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2. Goodall J. "A plea for chimps." New York Times Magazines, May 17 (1987)
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