Whither go the AIDS treatments?

Whither Go the AIDS Treatments?

Will ribavirin and ampligen be usedsomeday to routinely treat those with AIDS? Reports last week included the two drugs in a cornucopia of therapy possibilities, but it was evident that naming these, or any other drug, as acceptable treatments for AIDS will be a steady but slow process.

The drug ribavirin--subject of conflictingreports at last week's Third International Conference on AIDS in Washington, D.C.--is the most up-to-date case of a potential treatment awaiting final verdicts on its efficacy. In late 1984, researchers at the Centers for Disease Control in Atlanta reported that this known antiviral agent was effective in vitro against a virus possibly connected to AIDS (SN: 1/5/85, p.7). Ribavirin has not yet been approved for AIDS treatment in the United States, although recent changes in federal policy have shortened the experimental-drug approval process. Those changes were initiated by the approval of azidothymidine (AZT), currently the only AIDS drug clinically available in the United States (SN: 3/28/87, p.198).

After human clinical trials showed thatribavirin is relatively nontoxic, testing of the drug's effectiveness began last year, producing last week's contradictory results. "I don't know whether [ribavirin] works or not, but there are three or four pieces of preliminary evidence . . . that suggest it may have a benefit,' Clyde S. Crumpacker said in an interview. He described a study, begun last July, by his group at Harvard Medical School and Beth Israel Hospital in Boston.

That preliminary study tested whetherprolonged use of ribavirin would extend the lives of eight severely ill AIDS patients. In the six surviving patients, the drug thus far has prevented recurrences of pneumocystic pneumonia, a frequent cause of death in AIDS patients. (Although AIDS-related, the two deaths were not due to infection.) In seven of 10 untreated patients, the opportunistic lung infection reappeared within an average of 6.5 months, says Crumpacker.

Scientists elsewhere have concludedthat prolonged ribavirin therapy can prevent the progression from lymphadenopathy (swollen lymph nodes) to AIDS in men immunosuppressed by the AIDS virus. Researchers at the University of Texas in Houston, the University of Southern California in Los Angeles, Cornell University in Ithaca, N.Y., and University of Miami (Fla.) performed the study, which included about 160 men who were infected with the AIDS virus but had not developed AIDS. According to P.W.A. Mansell of the University of Texas, during the six-month test period, none of the patients receiving 800 milligrams daily developed AIDS, whereas 11 percent of those taking 600 mg/da and 18 percent taking placebos did develop the disease.

However, Food and Drug Administrationhead Frank E. Young attacked these results during the meeting. "Regretfully,' he said, "at this point we [the FDA] cannot find any evidence of effectiveness [of ribavirin].' (The drug's manufacturer, ICN Pharmaceuticals of Costa Mesa, Calif., was reprimanded late last month by the FDA for claims, based on this study, about the drug's efficacy. A similar ribavirin study at Johns Hopkins University in Baltimore and George Washington University in Washington, D.C., found "no statistically significant decline in progression to AIDS within 28 weeks' with ribavirin treatment, Andrew Vernon of Johns Hopkins said last week.

While ribavirin meets obstacles, anotherdrug has entered the AIDS treatment race. Researchers at several centers in the United States, including Hahnemann University in Philadelphia, report in the June 6 LANCET that a drug called ampligen apparently plays a double role in restoring immune function and controlling AIDS virus (HIV) replication in patients. Made by mismatching periodic regions on a double-stranded RNA, the drug is thought to have broad cellular effects, including induction of antiviral enzyme production and release of factors like interferon.

In a pilot study of 10 patients with AIDSor AIDS-related syndromes, a multitude of changes were observed in both HIV numbers and immune response capability, say the authors. For example, in treated patients, levels of certain T lymphocytes and antibodies that fight HIV infection were either maintained or increased during the study--which lasted seven to 18 weeks, depending on the patient. Also, cellular immunity apparently improved, as did some symptoms like fatigue. However, given the preliminary nature of the study, the authors say it is too early to tell whether ampligen will "affect disease progression or survival' in AIDS patients.