title: Presence of Tablet Remnants of Nevirapine Extended-Release in Stools and Its Impact on Virological Outcome in HIV-1-Infected Patients: A Prospective Cohort Study.
abstract: BACKGROUND
  Nevirapine extended-release (NVP-XR) taken once daily remains an effective antiretroviral agent for patients infected with HIV-1 strains that do not harbor resistance mutations. Presence of tablet remnants of NVP XR in stools was reported in 1.19% and 3.05% of subjects in two clinical trials. However, the prevalence may have been underestimated because the information was retrospectively collected in the studies.
  
  
  METHODS
  Between April and December 2014, we prospectively inquired about the frequency of noticing tablet remnants of NVP XR in stools in HIV-1-infected patients who switched to antiretroviral regimens containing NVP XR plus 2 nucleos(t)ide reverse-transcriptase inhibitors. Patients were invited to participate in therapeutic drug monitoring of plasma concentrations of NVP 12 or 24 hours after taking the previous dose (C12 and C24, respectively) of NVP XR using high-performance liquid chromatography. The information on clinical characteristics, including plasma HIV RNA load and CD4 lymphocyte count, at baseline and during follow-up was recorded.
  
  
  RESULTS
  During the 9-month study period, 272 patients switched to NVP XR-based regimens and 60 (22.1%) noticed tablet remnants of NVP XR in stools, in whom 54.2% reported noticing the tablet remnants at least once weekly. Compared with patients who did not notice tablet remnants, those who noticed tablet remnants had a higher mean CD4 lymphocyte count (629 vs 495 cells/mm3, P = 0.0002) and a similar mean plasma HIV RNA load (1.57 vs 1.61 log10 copies/mL, P = 0.76) on switch. At about 12 and 24 weeks after switch, patients who noticed tablet remnants continued to have a similar mean plasma HIV RNA load (1.39 vs 1.43 log10 copies/mL, P = 0.43; and 1.30 vs 1.37 log10 copies/mL, P = 0.26, respectively), but had a lower median NVP C12 (3640 vs 4730 ng/mL, P = 0.06), and a similar median NVP C24 (3220 vs 3330 ng/ml, P = 0.95) when compared with those who did not notice tablet remnants.
  
  
  CONCLUSIONS
  The presence of tablet remnants of NVP XR in stools is not uncommon in HIV-1-infected Taiwanese patients receiving NVP XR-based antiretroviral regimens, which does not have an adverse impact on the virological and immunological outcomes.
authors.affiliation: Department of Internal Medicine, Lotung Poh-Ai Hospital, Lo-Hsu Foundation, Inc., I-Lan, Taiwan.
authors.forename: Yi-Chieh
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Department of Pharmacy, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Graduate Institute of Clinical Pharmacy, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Shu-Wen
authors.initials: SW
authors.lastname: Lin
authors.affiliation: Department of internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Mao-Yuan
authors.initials: MY
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Sui-Yuan
authors.initials: SY
authors.lastname: Chang
authors.affiliation: Department of Pharmacy, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; School of Pharmacy, National Taiwan University, Taipei, Taiwan.
authors.forename: Ching-Hua
authors.initials: CH
authors.lastname: Kuo
authors.affiliation: Department of internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Center of Infection Control, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Wang-Huei
authors.initials: WH
authors.lastname: Sheng
authors.affiliation: Department of internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Szu-Min
authors.initials: SM
authors.lastname: Hsieh
authors.affiliation: Department of internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Hsin-Yun
authors.initials: HY
authors.lastname: Sun
authors.affiliation: Center of Infection Control, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Hsi-Yen
authors.initials: HY
authors.lastname: Chang
authors.affiliation: Department of internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Mon-Ro
authors.initials: MR
authors.lastname: Wu
authors.affiliation: Department of internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Wen-Chun
authors.initials: WC
authors.lastname: Liu
authors.affiliation: Center of Infection Control, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Pei-Ying
authors.initials: PY
authors.lastname: Wu
authors.affiliation: Center of Infection Control, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Shang-Ping
authors.initials: SP
authors.lastname: Yang
authors.affiliation: Center of Infection Control, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Jun-Yu
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: Center of Infection Control, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Su
authors.affiliation: Center of Infection Control, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Yi-Zhen
authors.initials: YZ
authors.lastname: Luo
authors.affiliation: Department of internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; China Medical University, Taichung, Taiwan.
authors.forename: Chien-Ching
authors.initials: CC
authors.lastname: Hung
authors.affiliation: Department of internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Shan-Chwen
authors.initials: SC
authors.lastname: Chang
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000302:isolation & purification; D065546:Drug Liberation; D005243:Feces / Q000737:chemistry; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity; D006801:Humans; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000008:administration & dosage* / Q000302:isolation & purification; D013607:Tablets / Q000008:administration & dosage / Q000302:isolation & purification; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D013607:Tablets; D019829:Nevirapine