ICAAC: Gains in limb fat and CD4 counts continue three years after switching from d4T to tenofovir

Three years after switching from d4T (stavudine, Zerit) to tenofovir (Viread) in an otherwise stable regimen, participants in the Gilead 903 study have maintained virologic suppression and continue to see increases in CD4 cell counts and limb fat, although the rate of limb fat gain has decreased considerably from the dramatic gains seen at two years. The results were presented as a poster at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, held this week in Chicago.

Study 903 is an ongoing Phase III trial composed of two phases. The first phase, now completed, was a 144-week randomised double-blind comparison of d4T to tenofovir, in addition to 3TC (lamivudine, Epivir) and efavirenz (Sustiva) in both study arms. Both arms were placebo-controlled; i.e., participants received placebo d4T or tenofovir in addition to whichever active drug they were taking. Results of this comparison phase were published in 2004.

In the ongoing open-label phase of the trial (903E), participants from Argentina, Brazil and the Dominican Republic are receiving tenofovir, 3TC and efavirenz, with analyses comparing those who switched from d4T to tenofovir to those who have continued tenofovir from the first study phase. This open-label phase is intended to run for 336 weeks (close to seven years) from the original initiation of treatment.

This report compared the two groups at 144 weeks after the treatment switch. At the time of the switch, the "switch" group consisted of 85 participants, 60% male, 64% white, mean age 37 years, with mean CD4 cell counts of 650 cells/mm³. All were virologically suppressed with viral loads below 400 copies/ml, and all but one (99%) had viral loads below 50 copies/ml.

At 144 weeks, of the initial 85 switched patients, eight had discontinued, all but one due to withdrawal of consent or being lost to follow-up. One patient discontinued due to abnormal renal function. (There were no discontinuations due to virologic failure.) No clinical abnormalities in serum phosphorus or creatinine levels, of any grade, have been observed in these 85 patients.

All of the patients still under follow-up have maintained viral loads

Significant decreases were observed from the time of switch to week 144 in fasting total cholesterol (mean change: -22 mg/dl, p

At time of switch, mean limb fat was 4.6 kg but by 144 weeks, had increased significantly to 5.8 kg (pEighth International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV in San Francisco had shown that, two years after switching from d4T to tenofovir, limb fat levels rose from 4.6 to 5.5 kilograms in those who switched – a gain of 0.9 kilogram. No significant changes in limb fat had been detected in the tenofovir continuation group. This represents a 0.45 kg increase per year over the first two years, and a somewhat smaller 0.3 kg increase in the third year.

The researchers concluded that, "in virologically suppressed patients, switching d4T to tenofovir as part of a once-daily regimen with 3TC and efavirenz resulted in maintenance of virologic suppression and continued CD4 cell increases through 144 weeks. Significant improvements in limb fat and fasting lipid parameters were observed."