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The 10 year safety and efficacy of tenofovir disoproxil fumarate (TDF)-containing once-daily highly active antiretroviral therapy (HAART)

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Journal of the International AIDS Society201013 (Suppl 4) :P86

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  • Peripheral Neuropathy
  • Lamivudine
  • Tenofovir
  • Efavirenz
  • Stavudine


Study 903 was a Phase III randomized double-blind (DB) 3 year study comparing TDF to stavudine (d4T) each in combination with lamivudine (3TC) and efavirenz (EFV) in HIV-1 infected antiretroviral naïve patients. TDF was associated with durable efficacy and safety (better lipid profile, and less lipodystrophy and peripheral neuropathy). A subset of these patients now provides 10 years of longitudinal efficacy and safety data of TDF-containing once-daily HAART.


Subjects in Argentina, Brazil, and the Dominican Republic who completed the 3 year DB period of study were eligible to roll-over into an open-label (OL) study (Study 903E) of the once-daily HAART regimen, TDF+3TC+EFV. At DB baseline 86 subjects were randomized to TDF (62% male, 70% white, mean age 33 yrs, mean HIV RNA=4.9 log10 c/mL, and mean CD4 count=299 cells/mm3). At OL baseline, 85 subjects (60% male, 64% white, mean age 37 yrs, median CD4=621 cells/mm3) switched from d4T to TDF. The results reflect only the period of TDF exposure.


See Table 1

Table 1


TDF/TDFα (n=86)

D4T/TDFα (n=85)

Weeks on HAART/TDF



HIV RNA < 50 (copies/mL) at Week 480 (ITT, M=F)



HIV RNA < 50 (copies/mL) at Week 480 (ITT, M=E)



Change in Mean (SD) CD4, cells/mm3

545 (287)

180 (290)

Drug-related Adverse Events (Grades 1-4)



Change in Mean (SD) Creatinine Clearance, mL/minβ

+2.5 (23.4)

-10.7 (22.6)

Median Limb Fat at Year 10, kg



Percent Change in Mean (SD) Spine BMDχ

-2.44 (5.08)δ

0.04 (4.72)

Percent Change in Mean (SD) Hip BMD

-2.94 (4.95)δ

-1.86 (4.67)δ

Discontinuations during open-label extension

25 (29.1%)

19 (22.4%)

Adverse event

2 (2.3%)

2 (2.4%)

Suboptimal virologic response

5 (5.8%)

1 (1.2%)

LTFUε, Nonadherent, Pregnancy, Consent Withdrawn, Death

13 (15.1%)

9 (10.6%)


5 (5.8%)

7 (8.2%)

αTDF/TDF results measured from DB BL; d4T/TDF from OL baseline; βEstimated by Cockcroft-Gault equation; χBone mineral density; δp<0.01 by Wilcoxon Signed Rank Test; εLost to follow-up


Antiretroviral-naïve subjects who received TDF-containing once-daily HAART for up to 10 years demonstrated sustained virologic and immunologic benefit, improved limb fat, stable renal function, and their BMD remained stable after a clinically insignificant decrease that occurred during the first year of TDF therapy.

Authors’ Affiliations

Fundacion Centro Estudios Infectologicos, Buenos Aires, Argentina
Hospital Guilherme Álvaro, Santos, Brazil
Centro de Referencia e Treinamento DST/AIDS, Sao Paulo, Brazil
Brasilmed Assistência Médica e Pesquisas, Sao Paulo, Brazil
Gilead Sciences, Inc, Foster City, USA


© Madruga et al; licensee BioMed Central Ltd. 2010

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.