Hydroxychloroquine+ddI+Hydroxyurea Antiretroviral Trial, AIDS Research Alliance, Los Angeles
A small phase I/II trial of a new antiretroviral combination is now recruiting in Los Angeles. Hydroxychloroquine, a well-known malaria drug also used in treating rheumatoid arthritis and lupus, has shown modest anti-HIV activity both in laboratory studies, and in patients. It is much less active against HIV than the protease inhibitors, so it will not replace standard therapy; instead, the point of this trial is to find a regimen which is less expensive and more tolerable, for certain patients who need treatment but for one reason or another are not using standard drug combinations.This study was organized and is sponsored by the AIDS Research Alliance (formerly Search Alliance); shortly before enrollment began, Bristol Myers provided a grant to fully fund the study. Sanofi donated the hydroxychloroquine.
Because of the number of study visits required for tests, volunteers will probably need to live in the Los Angeles area in order to participate. A total of 18 volunteers can enter this trial, in three different cohorts:
Cohort A, little (less than 6 months) or no antiretroviral therapy, no previous use of ddI, CD4 count above 200, and viral load between 5,000 and 80,000;
Cohort B, patients who have failed antiretroviral therapy, and stopped it because of toxicity or failure to maintain viral suppression--with CD4 count over 100, viral load between 5,000 and 1,000,000, and no ddI use within the past year; and
Cohort C, patients who have abandoned HAART for personal reasons during the past six months, and have been off therapy for at least three months and not used ddI within the last year--with CD4 count greater than 200, viral load 5,000 to 250,000.
For more information, call Corigan Castro at 310-358-2429.
Note:
This study opened in September; we were reluctant to announce it because we were hearing fragmentary reports of serious cases of toxicity with certain ddI combinations, and did not know how to warn our readers properly. But now the new information about the ddI risks has been widely distributed (see AIDS Treatment News #331). While no one knows for sure, it is widely suspected that many of the problems may result from mitochondrial toxicity due to too much exposure to nucleoside analog drugs. Hydroxychloroquine, the new drug in this combination, is not a nucleoside analog and does not seem to have the same toxicities. Its major long-term risk is to the eyes, and ophthalmologic examinations are included in this study so that the drug can be discontinued if necessary.
Antiretroviral Activity of Hydroxychloroquine
Here is a partial list of pre-clinical1,2,3 and clinical4,5,6 papers on antiretroviral activity of hydroxychloroquine.
References
1. Boelaert JR and Sperber K, Antiretroviral treatment. The Lancet. October 10, 1998; volume 352, pages 1224-1225.
2. Sperber K, Kalb TH, Stecher VJ, Banerjee R, and Mayer L. Inhibition of human immunodeficiency virus type 1 replication by hydroxychloroquine in T cells and monocytes. AIDS Research and Human Retroviruses. 1993; volume 9, number 1, pages 91-98.
3. Boelaert JR, Sperber K, and Piette J. Chloroquine exerts an additive in vitro anti-HIV type 1 effect when associated with didanosine and hydroxyurea. AIDS Research and Human Retroviruses. September 20, 1999; volume 15, pages 1241-1247.
4. Sperber K, Louie M, Kraus T, and others. Hydroxychloroquine treatment in patients with human immunodeficiency virus type 1. Clinical Therapeutics. 1995; volume 17, number 4, pages 622-636.
5. Sperber K, Chiang G, Chen H, and others. Comparison of hydroxychloroquine with zidovudine in asymptomatic patients infected with human immunodeficiency virus type 1. Clinical Therapeutics. 1997; volume 19, number 5, pages 913-923.
6. Ornstein MH and Serber K. The antiinflammatory and antiviral effects of hydroxychloroquine in two patients with acquired immunodeficiency syndrome and active inflammatory arthritis. Arthritis & Rheumatism. January 1996; volume 39, number 1, pages 157-161.
