96-week results show tenofovir-including regimen has side-effect advantages over d4T regimen in treatment naïve patients

Graham McKerrow, HIV i-Base

Scientists in Germany, the USA, London and Brazil reported in a poster the 96-week preliminary interim results of a blinded, randomised study looking at the safety and efficacy of tenofovir disoproxil fumarate (TDF, Viread) vs stavudine (d4T, Zerit) when used in combination with lamivudine (3TC, Epivir) and Efavirenz (EVF, Sustiva) in ARV-naïve patients.

The researchers, including Dr A Cheng of Gilead Sciences, who produce TDF, concluded that high proportions of patients in both arms of the study achieved HIV RNA <400 and <50 c/mL as well as significant increases in their CD4+ cell count.

They further concluded that the TDF arm showed significantly fewer toxicities associated with mitochondrial dysfunction, a better total fasting lipid profile, lower use of lipid lowering agents and more limb fat and weight gain. Both arms showed a similar renal safety profile.

Six hundred ART-naïve patients were randomised into the two treatment arms for a 144-week study.

The mean (95% CI) change in the fasting lipid profile for triglycerides was more than 100mg/dL in the d4T arm, but only 5mg/dL in the TDF arm (p<0.001). The mean (95% CI) weight change from baseline was more than 6lbs in the TDF arm and only about 1lb in the d4T arm (p=0.002). Total limb fat (DXA) was more than 17lbs in the TDF arm compared with about 11lbs in the d4T arm (p<0.001).

Selected toxicities associated with mitochondrial dysfunction through week 96

All Grades TDF+3TC+EFV d4T+3TC+EFV
Patients (%) n=299 n=301
with Events 11 (4%) 61 (20%)
8 (3%) 29 (10%)
Lipodystrophy* 3 (1%) 35 (12%)
Lactic Acidosis** 0 3 (1%)
Pancreatitis 0 0
Relative risk (95% CI) for toxicity (d4T/TDF) 5.5 (3.0, 10.3)
*Investigator defined
**p value <0.001


S Staszewski et al. Efficacy and safety of tenofovir DF (TDF) versus stavudine (d4T) when used with lamivudine and efavirenz in antiretroviral naive patients: 96-week preliminary interim results. 10th CROI, 10–14 February 2003, Boston. Abstract 564b.

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