Successful Treatment of Human Immunodeficiency Virus-Associated Thrombotic Microangiopathy with Eculizumab

Introduction: In the era of highly active antiretroviral therapy (HAART), thrombotic microangiopathy (TMA) is a rare manifestation of advanced human immunodeficiency virus (HIV) infection. Management of infection-associated TMA has traditionally included supportive care and antimicrobial agents, rather than anti-complement therapy such as eculizumab. Case Description: A 62-yo man with advanced HIV and chronic kidney disease stage 3B presented with 3 days of abdominal pain, vomiting, and diarrhea. Laboratory workup revealed severe thrombocytopenia, hemolytic anemia (with schistocytes on peripheral smear), acute kidney injury (AKI), ADAMTS13 activity of 72%, uncontrolled HIV (CD4 count 61 cells/ml, HIV viral load > 10 million copies/ml) (Table 1). A broad infectious workup revealed norovirus GI/GII and influenza A H3 infections and was otherwise negative including for Shiga-toxin producing Escherichia coli. Complement factor H autoantibody testing was negative, and he declined genetic testing for complement-mediated TMA risk genes. On day 3, he was started on eculizumab and hemodialysis. On day 8, HAART was resumed. All laboratory parameters improved dramatically by day 10, and hemodialysis was stopped on day 26. He received 5 doses of eculizumab while hospitalized and was discharged on day 31 with resolution of AKI and hemolysis. He was transitioned to maintenance ravulizumab post-discharge, and kidney function remained stable at least 2 weeks after original presentation. Discussion: HIV-associated TMA is well-recognized but only rarely reported to be successfully treated with eculizumab, as our case illustrates. The underlying pathophysiology and optimal duration of anti-complement therapy for this indication is unknown and warrants further investigation. Table 1. Laboratory values throughout clinical course - Day 1 (admission) Day 3 (prior to HD and eculizumab) Day 10 (1 week after eculizumab, on HD) Day 31 (hospital discharge, off HD) Day 55 (two weeks post-discharge, off HD) Hemoglobin (g/dl) 12.1 5.7 7.3 8.3 9.4 Platelets (x103/ul) 5 11 90 129 152 Creatinine (mg/dl) 6.99* 9.40 5.68 2.82 3.62 Blood urea nitrogen (mg/dl) 100 162 62 73 43 Haptoglobin (mg/dl) < 20 < 20 63 94 161 Lactate dehydrogenase (U/L) 2769 1900 911 260 224 Bilirubin (mg/dl) 1.2 1.5 0.6 0.2 NA HD, hemodialysis; NA, not available; *Baseline creatinine from 1 week prior was 2.1 mg/dl