A PHASE-II STUDY OF EFFECT OF ADDITION OF TRICHOSANTHIN TO ZIDOVUDINEIN PATIENTS WITH HIV DISEASE AND FAILING ANTIRETROVIRAL AGENTS

Patients infected with HIV, including those with AIDS-related complex and AIDS, and failing treatment with antiretroviral agents such as zid ovudine, have been evaluated following addition of trichosanthin to th e antiretroviral agent regimen. This ribosomal inhibitory protein is s pecifically cytotoxic for HIV-infected macrophages and lymphocytes. Ni nety-three patients were treated with trichosanthin, using a schedule of weekly, then monthly, intravenous injections of 1.2 mg of drug in c ombination with antiretroviral agents, usually zidovudine. Side effect s included myalgias, fevers, mild elevation in liver function tests, a nd mild-moderate anaphylactic reactions, which respond well to therapy with steroids and/or benedryl. Reversible mental status changes were noted in two patients, both receiving concomitant therapy with ddI. Cl inical responses to trichosanthin treatment were monitored primarily b y changes in laboratory parameters, particularly levels of CD4(+) T ly mphocytes. In the total population evaluated for efficacy (85 patients ) there was a significant increase in CD4(+) cell levels after initiat ion of trichosanthin therapy. A second analysis performed on 72 patien ts measured the rate of change of CD4(+) cells during therapy, using a n ''area under the curve'' analysis. During therapy there was a median increase of 1.2 cells/mm(3)/month. In patients in the top 25th percen tile, this increase was greater than 8.4 cells/mm(3)/month. In 59 of t he 72 patients, responses could also be monitored by comparing the rat e of loss of CD4(+) cell levels on antiretroviral agents (zidovudine o r ddI) alone, during the year prior to initiation of trichosanthin, to the rate of change when trichosanthin was added to the treatment regi men. During the period before trichosanthin treatment (311 +/- 11.7 da ys) the median loss of CD4(+) cells was 6.91 cells/mm(3)/month. Additi on of trichosanthin to the treatment regimen resulted in a median gain of 1.1 CD4(+) cells/mm(3)/month.