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Abstracts


AIDS and Opiates in a Monkey Model

Robert M. Donahoe, Ph.D.,
Emory University School of Medicine


Injection drug abuse (IDA) is a prominent cofactor in AIDS, and opiates are among the primary drugs involved. Opiates, themselves, modulate and compromise immunity and have been shown to modulate infections with HIV-1 in vitro. However, human clinical and epidemiological data have been equivocal in defining the relationship of opiate abuse and AIDS. Variable data are extant to support the notion that opiates exacerbate, retard, or cause no change in progression of AIDS. The main problem seems to relate to the complexity of the AIDS/IDA milieu so that epidemiological investigations are hampered in their ability to separate relevant variables. For example, we have found that opiates and cocaine, two drugs often shared in circumstances of IDA, can have counter-opposing effects on immune processes. This finding illustrates how the individual role of these two drugs in a complex IDA milieu would be difficult to discern.

Animal models have also been used to investigate the role of opiates in AIDS. Our laboratory has reported data from a small pilot study that opiates delivered regularly to rhesus monkeys infected with SIV, the simian analogue of human AIDS viruses, show slower progression of AIDS. Another lab has shown an opposite finding, however. Differences in the virus stocks used in these two studies and in drug-dosing regimens may account for differences in outcomes. Currently, we have expanded studies in this regard, using a much larger cohort of monkeys and better controls to determine how AIDS progression is affected by opiates. Also, from studies on effects of opiates on immune responses in monkeys, where AIDS viruses are not involved, we have learned that opiates can have both stabilizing and de-stabilizing immune effects, depending on the circumstances of drug dosing. Accordingly, we have hypothesized that opiates have the potential to both exacerbate and retard progression of AIDS depending on the context in which the drug is delivered as well as the viral status of the host and other host factors. Our ongoing studies are designed to test this hypothesis.

References

  1. Donahoe, RM, Nicholson JKA, Madden JJ, Donahoe F, Shafer DA, Gordon D, Bokos P, Falek A, Coordinate and independent effects of heroin, cocaine, and alcohol abuse on T-cell E-rosette formation and antigenic marker expression. Clin Immunol Immunopathol 41:254-264, 1986.

  2. Chuang RY, Blackbourne DJ, Chuang LF, Liu Y, Kilam KF, Jr. Modulation of simian AIDS by opioids. Adv Biosci 86:573-583, 1993.

  3. Donahoe RM, Byrd L, McClure HM, Fultz P, Brantley M, Marsteller F., Ansari AA, Wenzel D, Aceto M. Consequences of opiate-dependency in a monkey model of AIDS. Adv Exp Med Biol 335:21-28, 1993.

  4. Donahoe RM, Vlahov D. Opiates as potential cofactors in progression of HIV-1 infections to AIDS. J Neuroimmunol 83:77-87, 1998.

  5. Sharpe CW. Pharmaconeuroimmunology, AIDS and other diseases. J Neuroimmunol 83:1-174, 1998.



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