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

Background

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.

Methods

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.

Results

See Table 1

Table 1

Conclusions

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.