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.
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Results
See Table 1
Table 1
TDF/TDFα (n=86) | D4T/TDFα (n=85) | |
|---|---|---|
Weeks on HAART/TDF | 480/480 | 480/336 |
HIV RNA < 50 (copies/mL) at Week 480 (ITT, M=F) | 63% | 64% |
HIV RNA < 50 (copies/mL) at Week 480 (ITT, M=E) | 92% | 96% |
Change in Mean (SD) CD4, cells/mm3 | 545 (287) | 180 (290) |
Drug-related Adverse Events (Grades 1-4) | 66% | 46% |
Change in Mean (SD) Creatinine Clearance, mL/minβ | +2.5 (23.4) | -10.7 (22.6) |
Median Limb Fat at Year 10, kg | 10.4 | 7.5 |
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LTFUε, Nonadherent, Pregnancy, Consent Withdrawn, Death | 13 (15.1%) | 9 (10.6%) |
Other | 5 (5.8%) | 7 (8.2%) |
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.
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