The first U.S. multi-center study examining the safety and effectiveness of a new drug, one that blocks replication of the AIDS virus, HIV, by inhibiting a regulatory protein called tat, has begun at four sites of the AIDS Clinical Trials Group (ACTG), a network supported by the National Institute of Allergy and Infectious Diseases.
The drug, Ro 24-7429, unlike the three antiretroviral drugs currently approved for AIDS therapy, zidovudine (AZT), dideoxyinosine (ddI) and dideoxycytidine (ddC), appears to halt HIV replication in cells already infected with HIV, not just prevent the initial infection of cells. Preliminary studies also have shown that HIV may be less likely to develop resistance to Ro 24-7429 than to AZT, ddI and ddC.
Ro 24-7429 stops HIV replication by interfering with the virus's ability to make tat protein. Along with proteins of the host cell infected by HIV, the tat protein is responsible for translating HIV's genetic material from RNA to DNA, which is necessary for replication. Without tat, the translation never occurs, new virus is not made, fewer cells are infected and opportunities for the virus to mutate and develop drug-resistance decrease.
Preliminary studies done at The Johns Hopkins School of Medicine found that patients tolerated Ro 24-7429 well with no related toxicities. These studies compared single and multiple doses of the drug to determine the drug's safety and how it is processed in the body.
The NIAID trial, ACTG 213, will enroll 96 men and women who are infected with HIV, and older than 12 years and have not taken any antiretroviral therapy, such as zidovudine (AZT), for 28 days prior to entering the study. The participants must have counts of the white blood cells, CD4 + T cells, that range from 50 to 500 cells per cubic millimeter of blood.
Sites for the phase I-II trial include case western reserve University in Cleveland, Ohio, Harvard University in Boston, MA, Johns Hopkins in Baltimore MD, and University Of California at San Diego.
In the NIAID study, investigators will compare four groups of 24 patients who will receive for 12 weeks either Ro 24-7429 in doses of 25 milligrams (mg), 50 mg. Or 100 mg. Every eight hours or will receive 200 mg of AZT every eight hours or a body weight-dependent dose of (ddI) every 12 hours. For those individuals receiving Ro 24-7429, neither the investigators nor the participants will know the dose given.
At the end of 12 weeks, physicians will give the highest tolerated dose of Ro 24-7429 to patients who received AZT or ddI. These patients will continue on AZT or ddI as well.
Hoffman-LaRoche, Inc. will supply the drug for the study. People interested in more information about the trial can call 1-800- TRIALS-A.