amphotericin-b and efavirenz

The burden of Cryptococcus neoformans in cerebrospinal fluid (CSF) predicts clinical outcomes in human immunodeficiency virus (HIV)-associated cryptococcal meningitis (CM) and is lower in patients on antiretroviral therapy (ART). This study tested the hypothesis that initiation of ART during initial treatment of HIV/CM would improve CSF clearance of C. neoformans.. A randomized treatment-strategy trial was conducted in Botswana. HIV-infected, ART-naive adults aged≥21 years initiating amphotericin B treatment for CM were randomized to ART initiation within 7 (intervention) vs after 28 days (control) of randomization, and the primary outcome of the rate of CSF clearance of C. neoformans over the subsequent 4 weeks was compared. Adverse events, including CM immune reconstitution inflammatory syndrome (CM-IRIS), and immunologic and virologic responses were compared over 24 weeks.. Among 27 subjects enrolled (13 intervention and 14 control), [corrected] the median times to ART initiation were 7 (interquartile range [IQR], 5–10) and 32days (IQR, 28–36), respectively. The estimated rate of CSF clearance did not differ significantly by treatment strategy (-0.32 log10 colony-forming units [CFU]/mL/day±0.20 intervention and -0.52 log10 CFUs/mL/day (±0.48) control, P=.4). Two of 13 (15%) and 5 of 14 (36%) subjects died in the intervention and control arms, respectively (P=0.39). Seven of 13 subjects (54%) in the intervention arm vs 0 of 14 in the control arm experienced CM-IRIS (P=.002).. Early ART was not associated with improved CSF fungal clearance, but resulted in a high risk of CM-IRIS. Further research on optimal incorporation of ART into CM care is needed.. NCT00976040.

Topics: Adenine; Adult; AIDS-Related Opportunistic Infections; Alkynes; Amphotericin B; Anti-HIV Agents; Antifungal Agents; Antiretroviral Therapy, Highly Active; Benzoxazines; Colony Count, Microbial; Cyclopropanes; Deoxycytidine; Emtricitabine; Female; Humans; Immune Reconstitution Inflammatory Syndrome; Male; Meningitis, Cryptococcal; Organophosphonates; Survival Analysis; Tenofovir; Treatment Outcome

Penicillium marneffei (P. marneffei) infection usually occurs with skin, bone marrow, lung or hepatic involvement. However, no cases of P. marneffei infection with chylous ascites have been reported thus far. In this report, we describe the first case of acquired immune deficiency syndrome (AIDS) which has been complicated by a P. marneffei infection causing chylous ascites. We describe the details of the case, with an emphasis on treatment regimen. This patient was treated with amphotericin B for 3 mo, while receiving concomitant therapy with an efavirenz-containing antiretroviral regimen, but cultures in ascitic fluid were persistently positive for P. marneffei. The infection resolved after treatment with high-dose voriconazole (400 mg every 12 h) for 3 mo. P. marneffei should be considered in the differential diagnosis of chylous ascites in human immunodeficiency virus patients. High-dose voriconazole is an effective, well-tolerated and convenient option for the treatment of systemic infections with P. marneffei in AIDS patients on an efavirenz-containing antiretroviral regimen.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Alkynes; Amphotericin B; Anti-Retroviral Agents; Antifungal Agents; Benzoxazines; Chylous Ascites; Cyclopropanes; Diagnosis, Differential; Humans; Male; Middle Aged; Mycoses; Penicillium; Pyrimidines; Sepsis; Triazoles; Voriconazole