Trial Halted as Microbicide Increases HIV Risk

ARLINGTON, Va., Feb. 1 -- For the second time, efforts to create a topical microbicide that would protect against HIV transmission during sex have ended in failure.

Two major clinical trials of a compound called Ushercell (cellulose sulfate) were halted yesterday after a data review in one of them showed the compound increased the risk of HIV infection, rather than reducing it.

The disappointing results recall the outcome of a clinical trial of the spermicide nonoxynol-9, which is used in combination with a diaphragm to prevent pregnancies.

But when used as an HIV preventive, the substance actually increased the risk of infection by 50%, researchers reported during the 2000 International AIDS Conference in Durban, South Africa.

Ushercell was being tested in three African countries and India by CONRAD, a reproductive health organization here, and in Nigeria by Family Health International of Research Triangle Park, N.C.

CONRAD said its data safety monitoring committee had found evidence that the substance was increasing the risk of infection -- although no numerical details were given -- and had recommended halting the trial.

The outcome was "unexpected and disappointing," said Lut Van Damme, M.D., Ph.D., the principal investigator of the CONRAD trial. Ironically, Dr. Van Damme was also a leading investigator on the nonoxynol-9 study.

Family Health International followed CONRAD's lead as a precautionary measure, although a spokesman said its data monitoring committee had seen no evidence of a higher HIV risk.

"In Nigeria we did not find any evidence of greater risk of HIV infection," Vera Halpern, M.D., the study's principal investigator. "But we also found no evidence that the product was effective in preventing HIV."

The finding of the CONRAD data committee was a surprise, because the compound had been extensively tested in 11 earlier safety and contraceptive trials with more than 500 participants in Africa, India, and the U.S.

"While the closing of these trials is a profound disappointment for the microbicide field, we cannot let it paralyze us," said Zeda Rosenberg, Sc.D., the CEO of the International Partnership for Microbicides, in Silver Spring, Md.

In the absence of either an AIDS vaccine or a curative therapy, Dr. Rosenberg said, "prevention is the only way out of this epidemic."

While consistent condom use has been shown to block transmission, those in the field say that many women in the developing world can not successfully demand that their partners were condoms. As a result, a microbicide, which could be used discreetly and under a women's control, is regarded as a vital tool.

Physicians seeking ways to block HIV transmission during sex must now pin their hopes on three other compounds in phase III clinical trials:

• Carraguard, a gel made from the seaweed derivative carrageenan, is being studied in three sites in Africa and results are expected by the end of this year.
• PRO 2000, being developed by Indevus Pharmaceuticals of Lexington, Mass., is being tested in two separate trials in Africa.
• In one of the PRO 200 trials, a third compound, BufferGel -- being developed by ReProtect Inc., of Baltimore -- is also being tested.