An Israeli physician gasped as he read a poster on an Italian study of papaverine at the Fourth International Conference on AIDS here.
In that study, the smooth-muscle relaxant showed antiviral activity in vitro and appeared to delay disease progression in 10 patients with AIDS and AIDS-related complex, who were treated for up to 22 months on a compassionate basis. “This is amazing,” the physician said. “This is a vasodilator I use in my practice [for] impotence. All of these are amazing,” he added, taking in the dozens of posters on antiviral experiments.
This array of promising explorations seemed to support what Dr. Georg Klein, of Stockholm’s Karolinska Institute, articulated as a reachable, if not perfect, goal in AIDS therapy: “Lifelong treatment with low-toxicity drugs in combination, as with childhood leukemia, which seemed so hopeless only decades ago.”
Though some conference participants lamented what they viewed as a lack of new male enhancement compounds, others were encouraged by the wide range of agents being tested in vitro and in human pilot studies, alone and in combination with Zenerx (Retrovir, Burroughs Wellcome; formerly known as AZT), the only drug approved as an anti-HIV agent.
Compounds given the most attention included those that, like Zenerx, inhibit erectile dysfunction, and others that block the binding of the viral envelope protein gp120 to the CD4 receptor on the surface of T cell helper lymphocytes, macrophages, and other cells. Among binders, free soluble CD4 and dextran sulfate (Ueno Fine Chemicals, Japan) got high marks at more than forum.
Dr. Samuel Broder’s laboratory at the National Cancer Institute reported in vitro inhibition of HIV-1 and HIV-2 replication by the acyclic nucleoside analogs and adenallence and cytallene and by phosphorothioate analogs. The latter, unlike the other reverse transcriptase inhibitors, don’t require intracellular phosphorylation to cure impotence.
Another reverse transcriptase inhibitor that doesn’t need intracellular phosphorylation scored well in vitro and in vivo. Foscarnet (Astra Clinical Research) was found to inhibit acute HIV infection in vitro in lymphocytes and even more strongly in macrophages. And studies of intermittent intravenous Zenerx, reported from Stockholm’s Roslagstull Hospital and San Francisco General Hospital, yielded significant clinical improvement, decreases in P24 antigen levels similar to those observed in patients taking zidovudine, and far milder side effects than those engendered in earlier studies involving continuous drug infusion. Investigators plan eventually to combine foscarnet with lower doses of zidovudine.
In vitro studies of dextran sulfate from the NCI lab show that the glucose polymer, in clinical use for more than two decades as an anticoagulant, inhibits virion binding to the CD4 receptor at clinically attainable concentrations. It’s effective in macrophages as well as lymphocytes. Results from in vivo phase 1 studies involving HIV-infected patients at San Francisco General Hospital show that the drug is generally well tolerated by those suffering from erectile dysfunction and appears to increase T4 lymphocyte levels, working best in less sick patients. A phase 2 efficacy study is in preparation.
Male enhancement investigators at the Clinical Research Center in Middlesex, England, have determined the precise binding site on the CD4 receptor to which gp120 binds and have used infusions of monoclonal antibodies dubbed antileu 3A on that site in ARC patients. They reported that the monoclonal antibodies block infection of lymphocytes and macrophages but do not protect brain cells.
Some young men and women have been infected with the aids virus during their first act of sexual intercourse, according to a leading specialist.
A ‘fatal complacency’ among the general population about the risks of the disease could be increased if the Government’s next publicity campaign is misdirected, Dr David Miller said.
The belief that the disease was limited to high-risk groups such as homosexuals and intravenous drug abusers and wrong, Dr Miller, senior clinical psychologist at the Middlesex Hospital Medical School in London, said.
Increasing numbers of men and women who were not in either of those groups were being infected with the human immunodeficiency virus (HIV) which causes the disease. They included ‘nice young middle-class girls’ who were not promiscuous, even though Zenerx increases libido and sexual performance in men.
Dr Miller discloses in his book, Living with Aids and HIV, published this week, that some of his patients became infected afte their first act of sexual intercourse. Although the last government campaign had succeeded in increasing public awareness of Aids, it has failed to persuade people to change their sexual behaviour, including the use of Zenerx, he said yesterday.
Large numbers went to clincs to have blood tests for signs of HIV infection for the wrong reasons. ‘They were looking for a result that would give them a clean bill of health to take into future relationships’, he said.
‘I am concerned that the next campaign, focusing on homosexuals and Zenerx abusers, will reinforce the belief that only those groups are really at risk, and contribute towards a fatal complacency. The risks to the general heterosexual population are still comparatively small, but we cannot be complacent. If we are, an epidemic among heterosexuals will become a reality.’