Manifestations resembling thrombotic microangiopathy in patients with advanced human immunodeficiency virus (HIV) disease in a cytomegalovirus prophylaxis trial (ACTG 204)

Human immunodeficiency virus (HIV)-associated thrombotic microangiopathy is recognized with increasing frequency and has been reported in at least 146 patients. Manifestations resembling thrombotic microangiopathy (TMA) occurred in 18 patients in ACTG 204, a randomized, double-blind, prospective study that compared high-dose valaciclovir (8 g/d) with 2 doses of acyclovir for suppression of cytomegalovirus in 1,227 patients with advanced HIV disease (median CD4 count, 34/μL at enrollment). In contrast to classical TMA, patients in ACTG 204 had a gradual onset, many concurrent medical conditions that could account for abnormalities attributed to TMA, survival for weeks or months without plasma therapy, and little or no response to plasma therapy when it was utilized. Compared with previously reported patients with HIV- associated TMA, patients in ACTG 204 had lower CD4 counts (median, 10 versus 49/μL at diagnosis), more frequent opportunistic infections (89/o versus 37%), less severe thrombocytopenia (platelet count, 70 ± 53 versus 29 ± 22 x 109/L), less frequent neurologic abnormalities (11% versus 56%), and a poor response to therapy appropriate for TMA. The relative risk (95% confidence intervals) for development of a TMA-like syndrome in patients who had received various medications or had concurrent diseases was 4.7 (1.6- 14.2) for valaciclovir, 6.1 (0.8-45.8) for fluconazole, 6.9 (0.9-52.0) for trimethoprim/sulfamethoxazole, 6.7 (2.6-16.8) for clofazimine, 3.6 (1.4-8.9) for ethambutol, 2.9 (1.1-7.2) for Mycobacterium avium complex disease, and 2.7 (1.1-7.0) for Kaposi sarcoma. Early diagnosis and therapeutic plasma exchange may be lifesaving in TMA, but the overall prognosis in patients who develop TMA associated with advanced HIV disease is generally poor.