title: Efavirenz versus nevirapine in current clinical practice: a prospective, open-label observational study.
abstract: An open-label, observational, prospective 18-month survey was conducted to compare the efficacy and tolerability of the 2 available nonnucleoside reverse transcriptase inhibitors (NNRTIs) in all possible indications of current clinical practice. A broad range of clinical and laboratory variables accounting for drug efficacy and tolerability (with special emphasis on metabolic and hepatic toxicity) were measured in 287 evaluable patients treated with efavirenz, compared with 258 subjects taking nevirapine for 18 months. A separate efficacy analysis was performed in 154 antiretroviral-naive subjects, 298 patients experienced with 2-7 prior anti-HIV lines who abandoned protease inhibitors (PIs), and 103 subjects entering a salvage regimen containing at least 4 drugs, including PIs. Antiretroviral-naive patients experienced greater efavirenz activity at 3-12 months (maximum HIV RNA drop =-2.4 log(10) copies/mL), associated with a significantly higher rate of complete viral suppression, while immunologic results proved significant only after 6-9 months. When assessing experienced patients and those on rescue regimens, a similar and progressively blunted laboratory response was achieved, on the ground of a worse baseline virologic and immunologic profile, and duration of prior anti-HIV therapy. Both first-month (4.2 and 4.3% for efavirenz and nevirapine, respectively) and overall discontinuation rates (11.5 and 12%, respectively) proved similar, but a profound difference emerged as to the different spectrum of untoward events: central nervous system (CNS) disturbances, persisting metabolic abnormalities, and possibly gynecomastia and laboratory pancreatic abnormalities for efavirenz vs. immediate allergy and increased hepatotoxicity (regardless of chronic infection with hepatitis B or C virus and methadone use) for nevirapine. A limited virologic and immunologic advantage of efavirenz was observed in the first 12-month assessment of antiretroviral-naive patients, whereas all other examined situations did not disclose relevant efficacy differences between efavirenz and nevirapine throughout the 18-month comparison. Although the short- and long-term toxicity and withdrawal rates of the 2 drugs were comparable, the different pathways prompting allergic, metabolic, liver, and CNS disturbances observed with NNRTIs deserve careful investigation, to prevent toxicity of these relevant antiretroviral compounds.
authors.affiliation: Department of Clinical and Experimental Medicine, Division of Infectious Diseases, University of Bologna "Alma Mater Studiorum," S. Orsola Hospital, Bologna, Italy. manfredi@med.unibo.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Manfredi
authors.forename: Leonardo
authors.initials: L
authors.lastname: Calza
authors.forename: Francesco
authors.initials: F
authors.lastname: Chiodo
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D048588:Benzoxazines; D018791:CD4 Lymphocyte Count; D002493:Central Nervous System Diseases / Q000209:etiology; D003521:Cyclopropanes; D005260:Female; D005500:Follow-Up Studies; D006177:Gynecomastia / Q000209:etiology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology; D008107:Liver Diseases / Q000209:etiology; D008297:Male; D008659:Metabolic Diseases / Q000209:etiology; D019829:Nevirapine / Q000009:adverse effects / Q000627:therapeutic use*; D010078:Oxazines / Q000009:adverse effects / Q000627:therapeutic use*; D010182:Pancreatic Diseases / Q000209:etiology; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D010078:Oxazines; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; C098320:efavirenz