Long-term treatment with tenofovir does not appear to be associated with fat loss in people with HIV, according to five-year data from a major study sponsored by manufacturer Gilead presented this week at the Eighth International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV in San Francisco.
The study also showed that people who switched from d4T to tenofovir after three years of d4T treatment regained a significant amount of limb fat - almost one kilo after two years of tenofovir treatment.
Three-year results from this study were reported in the Journal of the American Medical Association in 2004.
The reports, presented as posters at the meeting, are likely to provide further reassurance to people with HIV and their doctors about the degree of risk of fat loss, or lipoatrophy, that comes with tenofovir treatment. The studies also show no significant change in kidney function and only marginal loss of bone mineral density after five years of tenofovir; both have been viewed as potential long-term side-effects of the drug.
Study 903 originally enrolled 602 individuals who were randomised equally to receive tenofovir or d4T. Ninety-two of the patients randomised to the tenofovir arm discontinued treatment compared to 100 of the 301 individuals randomised to receive d4T. Eighty-six patients in the tenofovir arm at trial sites in Latin America were rolled over to an open-label extension study that will follow participants for four years.
Similarly, 85 patients at Latin American trial sites who had been receiving d4T were switched to tenofovir, and will also be followed for four years.
In the tenofovir continuation group two virologic failures were observed by five years, with no virologic failures in the group who switched from d4T to tenofovir. One patient in the tenofovir group withdrew from the study due to an asymptomatic amylase elevation. No other serious adverse events such as Fanconi’s syndrome or renal abnormalities were reported.
No significant changes in kidney function were observed in the tenofovir continuation group, whether glomerular filtration rate was measured by Cockcroft-Gault score or MDRD, but the glomerular filtration rate fell very slightly in the group who switched from d4T to tenofovir (from 124 at the time of switching to 118 two years later by MDRD). This difference was statistically significant (pa GFR above 90 is considered normal.
In the tenofovir continuation group no significant change in limb fat was detected over three years, using DEXA scans to measure fat content (DEXA measurement began at the end of the second year of the 903 study). In the d4T group however, mean limb fat rose significantly after switching to tenofovir, from 4.6 to 5.5 kg (p
The d4T group also experienced small but significant declines in fasting triglycerides and fasting total cholesterol after switching (p
Bone mineral density at the hip and spine fell very slightly in the tenofovir continuation group, by 2.7% and 1.5% over five years, and this decline was not considered to be clinically relevant by the investigators, and may indeed reflect the normal degree of bone density loss seen with ageing. A slight decline in hip bone mineral density was recorded in the group that switched from d4T to tenofovir, but no change was seen at the spine.
Cassetti I et al. The safety and efficacy of tenofovir DF in combination with lamivudine and efavirenz through 5 years in antiretroviral-naïve patients. Eighth International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, San Francisco, poster 82, 2006.
Madruga JVR et al. Switch from stavudine to tenofovir DF in combination with lamivudine and efavirenz resulted in continued virologic suppression and improvement in lipoatrophy through 2 years in HIV-infected patients. Eighth International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, San Francisco, poster 29, 2006.