title: A phase I/II study of nevirapine for pre-exposure prophylaxis of HIV-1 transmission in uninfected subjects at high risk.
abstract: OBJECTIVE
  To evaluate the safety, tolerability, and trough levels of three pre-exposure prophylaxis regimens of nevirapine among HIV-1-uninfected subjects at high risk for HIV-1 infection.
  
  
  METHODS
  A phase I/II trial (HIVHOP 101) in which 33 such uninfected subjects received a 200 mg tablet of nevirapine once weekly (cohort A, n = 12), twice weekly (cohort B, n = 12), or every other day (cohort C, n = 9) for 12 weeks. Clinical signs/symptoms, laboratory parameters, and nevirapine trough levels were assessed at entry and at 1, 2, 4, 6, 9, and 12 weeks, with a follow-up sample at 16 weeks.
  
  
  RESULTS
  No subject experienced clinical symptoms attributed to nevirapine, including rash. There were no significant changes in liver enzyme levels from baseline to week 12 in the three cohorts, except for glutamyl transpeptidase in cohort B. Median nevirapine trough levels at weeks 1 and 12 were 119 ng/ml (range, < 25-205) and 135 ng/ml (range, < 25-1065), respectively, for cohort A, 569 ng/ml (range, 135-2641) and 431 ng/ml (range, 42-2454) for cohort B, and 1942 ng/ml (range, 1214-2482) and 943 ng/ml (range, 262-5281) for cohort C. No subject became HIV-1 antibody positive by week 16.
  
  
  CONCLUSIONS
  A single dose of nevirapine taken once weekly, twice weekly, or every other day for 12 weeks was safely tolerated by the subjects in this small study, and resulted in nevirapine levels well above the IC (inhibitory concentration of 50%: 10 ng/ml) over the 12-week period in nearly all evaluable subjects. (50)
authors.affiliation: Departments of Pathology and Medicine, Johns Hopkins University, Baltimore, Maryland 21287, USA.
authors.forename: J Brooks
authors.initials: JB
authors.lastname: Jackson
authors.forename: Scott
authors.initials: S
authors.lastname: Barnett
authors.forename: Estelle
authors.initials: E
authors.lastname: Piwowar-Manning
authors.forename: Linda
authors.initials: L
authors.lastname: Apuzzo
authors.forename: Charles
authors.initials: C
authors.lastname: Raines
authors.forename: Craig
authors.initials: C
authors.lastname: Hendrix
authors.forename: Fayez
authors.initials: F
authors.lastname: Hamzeh
authors.forename: Joel
authors.initials: J
authors.lastname: Gallant
mesh_terms: D019380:Anti-HIV Agents / Q000097:blood / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1; D006526:Hepatitis C / Q000201:enzymology; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D019829:Nevirapine / Q000097:blood / Q000627:therapeutic use*; D012309:Risk-Taking; D018709:Statistics, Nonparametric
chemical_list: D019380:Anti-HIV Agents; D019829:Nevirapine