title: A 72-week randomized study of the safety and efficacy of a stavudine to zidovudine switch at 24 weeks compared to zidovudine or tenofovir disoproxil fumarate when given with lamivudine and nevirapine.
abstract: BACKGROUND
  Due to superior long-term toxicity profiles, zidovudine (AZT) and tenofovir disoproxil fumarate (TDF) are preferred over stavudine (d4T) for first-line antiretroviral regimens. However, short-term d4T use could be beneficial in avoiding AZT-induced anaemia.
  
  
  METHODS
  We randomized (1:1:1) 150 treatment-naive Thai HIV-infected adults with CD4(+) T-cell count <350 cells/mm(3) to arm 1 (24-week GPO-VIR S30(®) [d4T plus lamivudine (3TC) plus nevirapine (NVP)] followed by 48-week GPO-VIR Z250(®) [AZT plus 3TC plus NVP]), arm 2 (72-week GPO-VIR Z250(®)) or arm 3 (72-week TDF plus emtricitabine [FTC] plus NVP). Haemoglobin (Hb), dual energy x-ray absorptiometry, neuropathic signs, estimated glomerular filtration rate (eGFR), CD4(+) T-cell count, plasma HIV RNA and adherence were assessed.
  
  
  RESULTS
  In an intention-to-treat analysis, mean Hb decreased from baseline to week 24 in arm 2 compared with arm 1 (-0.19 versus 0.68 g/dl; P=0.001) and arm 3 (0.48 g/dl; P=0.010). Neuropathic signs were more common in arm 2 compared with arm 3 (20.4 versus 4.2%; P=0.028) at week 24. There were no differences in changes in peripheral fat and eGFR from baseline to weeks 24 and 72 among arms. CD4(+) T-cell count increased more in arm 1 than arms 2 and 3 from baseline to week 24 (168 versus 117 and 118 cells/mm(3); P=0.01 and 0.02, respectively) but the increase from baseline to week 72 was similar among arms.
  
  
  CONCLUSIONS
  A 24-week d4T lead-in therapy caused less anaemia and greater initial CD4(+) T-cell count increase than initiating treatment with AZT. This strategy could be considered in patients with baseline anaemia or low CD4(+) T-cell count. If confirmed in a larger study, this may guide global recommendations on antiretroviral initiation where AZT is more commonly used than TDF.
authors.affiliation: South East Asia Research Collaboration with Hawaii, Bangkok, Thailand. Nittaya.P@SearchThailand.org
authors.forename: Nittaya
authors.initials: N
authors.lastname: Phanuphak
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
authors.forename: Nipat
authors.initials: N
authors.lastname: Teeratakulpisarn
authors.forename: Tanate
authors.initials: T
authors.lastname: Jadwattanakul
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kerr
authors.forename: Nitiya
authors.initials: N
authors.lastname: Chomchey
authors.forename: Piranun
authors.initials: P
authors.lastname: Hongchookiat
authors.forename: Pornpen
authors.initials: P
authors.lastname: Mathajittiphun
authors.forename: Suteeraporn
authors.initials: S
authors.lastname: Pinyakorn
authors.forename: Patcharawee
authors.initials: P
authors.lastname: Rungrojrat
authors.forename: Pairoa
authors.initials: P
authors.lastname: Praihirunyakit
authors.forename: Mariana
authors.initials: M
authors.lastname: Gerschenson
authors.forename: Praphan
authors.initials: P
authors.lastname: Phanuphak
authors.forename: Victor
authors.initials: V
authors.lastname: Valcour
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
authors.forename: Cecilia
authors.initials: C
authors.lastname: Shikuma
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D004032:Diet; D004334:Drug Administration Schedule; D057915:Drug Substitution; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage; D063065:Organophosphonates / Q000008:administration & dosage; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D018119:Stavudine / Q000008:administration & dosage; D000068698:Tenofovir; D016896:Treatment Outcome; D019562:Viral Load; D015215:Zidovudine / Q000008:administration & dosage
chemical_list: D006454:Hemoglobins; D063065:Organophosphonates; D019259:Lamivudine; D015215:Zidovudine; D019829:Nevirapine; D000068698:Tenofovir; D018119:Stavudine; D000225:Adenine