title: Long-term efficacy and safety of tenofovir disoproxil fumarate in HIV-1-infected adolescents failing antiretroviral therapy: the final results of study GS-US-104-0321.
abstract: BACKGROUND
  Reports of long-term tenofovir disoproxil fumarate (TDF) treatment in HIV-infected adolescents are limited. We present final results from the open-label (OL) TDF extension following the randomized, placebo (PBO)-controlled, double-blind phase of GS-US-104-0321 (Study 321).
  
  
  METHODS
  HIV-infected 12- to 17-year-olds treated with TDF 300 mg or PBO with an optimized background regimen (OBR) for 24-48 weeks subsequently received OL TDF plus OBR in a single arm study extension. HIV-1 RNA and safety, including bone mineral density (BMD), was assessed in all TDF recipients.
  
  
  RESULTS
  Eighty-one subjects received TDF (median duration 96 weeks). No subject died or discontinued OL TDF for safety/tolerability. At week 144, proportions with HIV-1 RNA <50 copies/mL were 30.4% (7 of 23 subjects with baseline HIV-1 RNA >1000 c/mL initially randomized to TDF), 41.7% (5 of 12 subjects with HIV-1 RNA <1000 c/mL who switched PBO to TDF) and 0% (0 of 2 subjects failed randomized PBO plus OBR with HIV-1 RNA >1000 c/mL and switched PBO to TDF). Viral resistance to TDF occurred in 1 subject. At week 144, median decrease in estimated glomerular filtration rate was 38.1 mL/min/1.73 m (n = 25). Increases in median spine (+12.70%, n = 26) and total body less head BMD (+4.32%, n = 26) and height-age adjusted Z-scores (n = 21; +0.457 for spine, +0.152 for total body less head) were observed at week 144. Five of 81 subjects (6%) had persistent >4% BMD decreases from baseline.
  
  
  CONCLUSIONS
  Some subjects had virologic responses to TDF plus OBR, and TDF resistance was rare. TDF was well tolerated and can be considered for treatment of HIV-infected adolescents.
authors.affiliation: From the *Instituto de Infectologia Emílio Ribas, São Paulo, Brazil; †Hospital Infantil Joana de Gusmão, Hospital DIA - Agronômica, Florianópolis, Brazil; ‡Instituto da Criança do Hospital das Clínicas da FMUSP, São Paulo, Brazil; §Faculdade de Medicina, UFMG, Belo Horizonte, Brazil; ¶Universidade Estadual de Campinas-UNICAMP, Campinas, Brazil; ‖Gilead Sciences, Foster City, California; and **Gilead Sciences, Cambridge, United Kingdom.
authors.forename: Marinella
authors.initials: M
authors.lastname: Della Negra
authors.forename: Aroldo Prohmann
authors.initials: AP
authors.lastname: De Carvalho
authors.forename: Maria Zilda
authors.initials: MZ
authors.lastname: De Aquino
authors.forename: Jorge Andrade
authors.initials: JA
authors.lastname: Pinto
authors.forename: Marcos Tadeu Nolasco
authors.initials: MT
authors.lastname: Da Silva
authors.forename: Kristen N
authors.initials: KN
authors.lastname: Andreatta
authors.forename: Bryan
authors.initials: B
authors.lastname: Graham
authors.forename: Ya-Pei
authors.initials: YP
authors.lastname: Liu
authors.forename: Erin K
authors.initials: EK
authors.lastname: Quirk
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects* / Q000379:methods*; D015519:Bone Density; D002648:Child; D004311:Double-Blind Method; D024882:Drug Resistance, Viral; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D063065:Organophosphonates / Q000009:adverse effects* / Q000627:therapeutic use*; D010919:Placebos / Q000008:administration & dosage; D012367:RNA, Viral / Q000097:blood; D000068698:Tenofovir; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D010919:Placebos; D012367:RNA, Viral; D000068698:Tenofovir; D000225:Adenine