Sodium pentosan polysulfate (PPS), an anti-HIV agent also exhibits synergism with AZT, lymphoproliferative activity, and virus enhancement.
Sodium pentosan polysulfate (PPS), a negatively charged polymer of beta-D-xylopyranose units, was evaluated for its anti-HIV effects in normal human peripheral mononuclear cells (PMNC) and its possible synergism with AZT. In the presence of 25 nM AZT, 2.0 micrograms/ml of PPS reduced HIV-1 replication 110-fold, compared with a 3.9- and 7-fold decrease in the presence of either drug individually. Surprisingly, at low (below 1 microgram/ml) concentrations of either PPS or dextran sulfate, an enhancement of virus production was observed. PPS was nontoxic, had a proliferative effect on uninfected and a protective effect on infected PMNC. Virus enhancement at low concentrations of PPS appeared to be linked to its lymphoproliferative effect. These findings suggest that the use of PPS and others such agents as monotherapy for AIDS might have deleterious effects. However, due to its marked synergism with AZT and its lymphoproliferative activities, PPS might prove to be a useful agent in therapeutic trials of AIDS if used in combination with less than the usual dosage of AZT.
Laboratory of Biochemical Genetics, National Institute of Mental Health, Neuroscience Center at Saint Elizabeths Hospital, Washington, DC 20032.
R
R
Anand
S
S
Nayyar
T A
TA
Galvin
C R
CR
Merril
L B
LB
Bigelow
D002240:Carbohydrate Sequence; D002470:Cell Survival; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D015683:Gene Products, gag / Q000276:immunology; D015488:HIV Antigens / Q000276:immunology; D016655:HIV Core Protein p24; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000187:drug effects; D010426:Pentosan Sulfuric Polyester / Q000008:administration & dosage / Q000494:pharmacology*; D011134:Polysaccharides / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors; D014758:Viral Core Proteins / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000008:administration & dosage / Q000494:pharmacology*
D015683:Gene Products, gag; D015488:HIV Antigens; D016655:HIV Core Protein p24; D011134:Polysaccharides; D018894:Reverse Transcriptase Inhibitors; D014758:Viral Core Proteins; D010426:Pentosan Sulfuric Polyester; D015215:Zidovudine