November 5, 2012
Dr. David Boulware, professor of infectious diseases and international medicine at the University of Minnesota in Minneapolis, advised that in treatment-naive HIV patients with cryptococcal meningitis, the meningitis should be treated until the patients' cerebrospinal fluid (CSF) is cleared of the infection before antiretroviral therapy (ART) is administered. Boulware was speaking at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy. He made these recommendations based on a study that examined ART and delayed ART in ART-naive HIV patients with cryptococcal meningitis in Uganda and South Africa.
The researchers studied 87 patients who were randomly assigned to an efavirenz and nucleoside reverse transcriptase inhibitor ART regimen 7-11 days after starting therapy for cryptococcal meningitis, with 0.7-1.0 mg/kg per day of amphotericin and 800 mg/day of fluconazole. Another 87 patients received an ART regimen 5 weeks or more after the start of treatment for cryptococcal meningitis, when amphotericin was discontinued and fluconazole was reduced to a lower dose.
The trial was stopped in April 2012, as researchers realized that early-ART patients were 1.7 times more likely than delayed-ART patients to die within six months. Six-month mortality was 42.5 percent (37 patients) in early ART and 27.6 percent (24 patients) in delayed ART. Although the mortality differences were driven by patients who entered the trial with altered mental status, and those who did not have strong CSF inflammatory responses, Boulware stated those who were not sick showed "no benefits and no trends of benefits" from early ART.
Boulware suggested starting ART around 3 to 4 weeks when the CSF is sterile. He also emphasized the importance of making sure the CSF culture is sterile before reducing the fluconazole. He recommended a longer wait for patients with little CSF inflammation, as well as those with altered mental status.
The trial was sponsored by the National Institute of Allergy and Infectious Diseases.