CATIE ANTI-HIV AGENTS: Syphilis drug dropped

ANTI-HIV AGENTS: Syphilis drug dropped

TreatmentUpdate40: February 1993
Sean Hosein

In 1990 researchers at The University of Pittsburgh reported that an arsenic compound, oxophenarsine, (Mapharsen(R)) was able to block HIV production in experiments with cells. Viral replication was suppressed in cells chronically infected with HIV. Drugs such as AZT, ddC and ddI cannot stop HIV replication in these cells. An HIV-infected cell can produce virus which can move from one cell to another infecting the previously uninfected cell. Such cell-to-cell infection continues despite the use of AZT and the presence of anti-viral antibodies. Researchers are thus testing thousands of compounds for their potential anti-HIV activity.

How It Works

Oxophenarsine was used in the pre-penicillin era for the treatment of syphilis. That an antibiotic can have anti-HIV activity is not surprising. Scientists in several laboratories in different countries have reported that antibiotic treatment of HIV-infected cells has prolonged their survival or prevented their death. It is thought that the antibiotics kill microorganisms called mycoplasma which may be a co-factor in the death of HIV-infected cells. Researchers working with the Parke-Davis company have recently completed laboratory experiments with oxophenarsine. According to their results oxophenarsine inhibits replication of HIV-l and HIV-2. The anti-viral activity of the drug varied depending on the type of cell used in the experiments. As well, to improve the efficiency of the drug's anti-viral action, higher concentrations of oxophenarsine were used but the drug appeared to cause some toxicity.

Problems

The Parke-Davis researchers did mention that oxophenarsine, when used to treat syphilis, had to be given intravenously because of poor absorption when administered orally. When used to treat syphilis, oxophenarsine was given to patients on an intermittent basis, otherwise arsenic concentrations would build up and cause toxicity. It is interesting that the researchers at Parke-Davis cite the poor oral absorption and the need for intravenous administration, in addition to its potential toxicity, as reasons not to pursue further testing of the drug for the treatment of HIV-infected people. Improvements in capsule technology since oxophenarsine was first used might make oral use of the drug possible. That anti-viral drugs can cause toxic side effects is not a recent problem and has certainly not stopped doctors from prescribing drugs such as AZT and ganciclovir. As oxophenarsine was introduced over 40 years ago there may also be issues relating to patent rights and thus potential profits. These issues were not discussed in the report from Parke-Davis.

REFERENCES:

1. Gupta P, B alachandran R, Thampatty P, et al. Oxophenarsine, an anti syphilis drug inhibits HIV-1-specific protein synthesis in acutely and persistently infected lymphocytes. AIDS Research and Human Retroviruses 1990:6(12):1417-1423.

2. Holland LE, Buthod JL, Kowal CD and Antonucci TK. Characterization of oxophenarsine as a potential antiviral agent for AIDS. AIDS Research and Human Retroviruses 1992;8(9):1717-1722.

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