Prophylactic clarithromycin to treat mycobacterium avium in HIV patients receiving zidovudine may significantly increase mortality by suppressing lymphopoiesis and hematopoiesis.
The increased mortality observed when human immunodeficiency virus (HIV)-infected individuals are treated with clarithromycin (CLA) as prophylaxis for disseminated infection with organisms of the Mycobacterium avium complex (MAC) suggests that CLA might possess immunosuppressive activities. To test this possibility, we assessed the immunological response of BALB/c mice following subchronic (28 days) oral administration of CLA alone or in combination with zidovudine (ZDV). Because normal hematopoiesis is needed to maintain the immune system, we also examined the effect of these drugs given individually or in combination on several hematological parameters. The major effect of administration of 500 mg/kg CLA was a marked decrease in the lymphocyte/neutrophil ratio, and the only evidence of hematotoxicity in mice treated with 240 mg/kg ZDV alone was mild macrocytic anemia. However, treatment with a combination of CLA and ZDV resulted in severe hematotoxicity, evidenced by a significant (p < 0.01) decrease in the number of circulating erythrocytes, neutrophils, and lymphocytes and a 67% drop in splenic cellularity (p < 0.01). Treatment with CLA or ZDV alone or both drugs in combination had no effect on lymphocyte function, determined by measuring the ex vivo proliferative activity of splenocytes in response to alloantigens or a B cell mitogen, lipopolysaccharide (LPS). However, because of the cellular depletion in the spleen, overall immune responses in this organ decreased significantly (p < 0.05) in mice treated with CLA plus ZDV. These data suggest that interactions between CLA and ZDV warrant further evaluation because these drugs are given in combination to persons with advanced HIV infection.
Freund
Yvonne R
YR
SRI International, Menlo Park, CA 94025, USA. yvonnerfreund@aol.com
Dousman
Linda
L
Mohagheghpour
Nahid
N
D017088:AIDS-Related Opportunistic Infections / Q000517:prevention & control*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D019380:Anti-HIV Agents / Q000633:toxicity*; D002460:Cell Line; D017291:Clarithromycin / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015658:HIV Infections / Q000401:mortality; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D038041:Lymphopoiesis / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D015270:Mycobacterium avium-intracellulare Infection / Q000517:prevention & control*; D015215:Zidovudine / Q000633:toxicity*
D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents; D015215:Zidovudine; D017291:Clarithromycin