title: Liver and renal safety of tenofovir disoproxil fumarate in combination with emtricitabine among African women in a pre-exposure prophylaxis trial.
abstract: BACKGROUND
  Safety of tenofovir disoproxil fumarate/emtricitabine (TDF-FTC) has been studied more extensively among HIV-infected patients than among HIV-uninfected people. Using data from a pre-exposure trial - FEM-PrEP -, we determined the cumulative probabilities of grade 1+ ALT, AST and creatinine and grade 2+ phosphorus toxicities; ALT/AST toxicities by baseline hepatitis B status; and change in mean creatinine, phosphorus, ALT and AST levels controlling for TDF-FTC adherence.
  
  
  RESULTS
  FEM-PrEP was a randomized, blinded, placebo-controlled trial of daily TDF-FTC among women in Africa. Enrolled women were in general good health, HIV antibody negative, 18 to 35 years old, hepatitis B surface antigen negative, and had normal hepatic and renal function at baseline. AST, ALT, phosphorus and serum creatinine were measured regularly throughout the trial. TDF-FTC concentrations were measured to assess adherence to TDF-FTC. The cumulative probabilities of grade 1+ creatininemia and grade 2+ phosphatemia toxicities were not statistically different between TDF-FTC and placebo arms. The cumulative probabilities of grade 1+ ALT and AST toxicities were higher among participants in the TDF-FTC arm than in the placebo arm (p = 0.03 for both). The proportions of grade 1+ and grade 2+ ALT or AST toxicities were significantly higher in participants who were hepatitis B virus surface antibody (HBsAb) positive than in those who were HBsAb-negative. Women with good adherence had higher mean change from baseline to week 4 in their AST levels (2.90 (0.37, 5.42); p = 0.025) than women with less than good adherence.
  
  
  CONCLUSIONS
  We did not observe a significant relationship between randomization to TDF-FTC and creatinine or phosphorus toxicities. Women randomized to TDF-FTC had higher rates of mild to moderate ALT/AST toxicities, especially women with prior hepatitis B virus exposure. We also observed a significant increase in AST from baseline to week 4 among women who had higher adherence to TDF-FTC during that interval.
  
  
  BACKGROUND
  #NCT00625404, February 19, 2008.
authors.affiliation: FHI 360, 1825 Connecticut Ave, Suite 800, NW, Washington, DC 20009, USA. JMandala@fhi360.org.
authors.forename: Justin
authors.initials: J
authors.lastname: Mandala
authors.forename: Kavita
authors.initials: K
authors.lastname: Nanda
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.forename: Irith
authors.initials: I
authors.lastname: De Baetselier
authors.forename: Jennifer
authors.initials: J
authors.lastname: Deese
authors.forename: Johan
authors.initials: J
authors.lastname: Lombaard
authors.forename: Fredrick
authors.initials: F
authors.lastname: Owino
authors.forename: Mookho
authors.initials: M
authors.lastname: Malahleha
authors.forename: Rachel
authors.initials: R
authors.lastname: Manongi
authors.forename: Douglas
authors.initials: D
authors.lastname: Taylor
authors.forename: Lut
authors.initials: L
authors.lastname: Van Damme
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives*; D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D019380:Anti-HIV Agents / Q000009:adverse effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D044383:Black People; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000209:etiology*; D003404:Creatinine / Q000097:blood; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000517:prevention & control; D006801:Humans; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced*; D063065:Organophosphonates / Q000009:adverse effects*; D010758:Phosphorus / Q000097:blood; D065129:Pre-Exposure Prophylaxis; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects*; D000068698:Tenofovir; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D003841:Deoxycytidine; D010758:Phosphorus; D000068698:Tenofovir; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000068679:Emtricitabine; D000225:Adenine