Rationale for a combined use of antiretroviral and immunomodulatory therapies in HIV infection.
To investigate a possible potentiation of Azidothymidine activity by immunomodulators, two in vitro models of HIV infection were analyzed. Peripheral blood lymphocytes on one hand, and cells from the CEM line on the other hand, were infected in vitro with HIV1 and reverse transcriptase activity was monitored daily in the cultures. When Azidothymidine was added, reverse transcriptase activity was significantly reduced. When Isoprinosine or Diethyldithiocarbamate was added in vitro, the reverse transcriptase was only slightly decreased (to a much less significant degree). When Azidothymidine was added together with either Isoprinosine or Diethyldithiocarbamate, a synergistic effect was observed with a very potent inhibition of reverse transcriptase activity. Before a possible application of such a combined therapy to patients, the pharmacokinetics of Azidothymidine was analyzed after the compound had been given alone or in combination with Isoprinosine. No alteration of pharmacokinetics was observed, suggesting that the immunomodulator will not alter the metabolism of the antiretroviral therapy in vivo, and may even enhance its biological activity, as it does in vitro.
Touraine
J L
JL
Faculté A. Carrel (Université Claude Bernard), INSERM U80, Hôpital Edouard Herriot, Lyon, France.
Sanhadji
K
K
Zerhouni
B
B
Livrozet
J M
JM
D002478:Cells, Cultured; D004050:Ditiocarb / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D007542:Inosine Pranobex / Q000008:administration & dosage*; D008297:Male; D012194:RNA-Directed DNA Polymerase / Q000032:analysis; D015215:Zidovudine / Q000008:administration & dosage* / Q000493:pharmacokinetics
D015215:Zidovudine; D004050:Ditiocarb; D012194:RNA-Directed DNA Polymerase; D007542:Inosine Pranobex