Switch to tenofovir better than change to abacavir?

Switching from stavudine or zidovudine to tenofovir may have some advantages over switching to abacavir, according to 48-week study results presented on Thursday at the 12th Conference on Retroviruses and Opportunistic Infections in Boston, Massachusetts. Trading stavudine or zidovudine for either tenofovir or abacavir led to gains in peripheral fat; however, more people had to discontinue abacavir than tenofovir, and lipid measures after 48 weeks favoured tenofovir.

Earlier research established that HIV-infected people with peripheral lipoatrophy can regain about one third of their lost fat in 2 years if they swap stavudine or zidovudine for abacavir (Martin) Because long-term studies of antiretroviral-naive people starting tenofovir showed little or no dwindling of arm or leg fat, Dr. Graeme Moyle of London’s Chelsea and Westminster Hospital and colleagues throughout Britain compared an abacavir switch with a tenofovir trade in 105 people with lipoatrophy.

The predominantly male and white study group had received a stable antiretroviral regimen for at least 24 weeks, had a viral load under 50 copies/mL, and had no kidney or liver problems. Most people in both treatment arms were not taking a protease inhibitor. Notably, the proportion of patients switching from stavudine to the new drug was 77% among those randomised to tenofovir compared with 59% among those randomised to abacavir. At study entry the groups did not differ in total body fat, trunk fat, or limb fat (limb fat: 3.0 kg in the tenofovir arm and 2.9 kg in the abacavir arm).

After 48 weeks, the tenofovir group gained a median 393 g of limb fat and the abacavir group added 316 g, a nonsignificant difference. Dr. Moyle calculated that study participants replaced 12% to 15% of lost peripheral fat during that time. Each group also experienced a “tiny proportional change” in abdominal fat.

But people tolerated tenofovir better than abacavir, and lipid measures improved significantly with tenofovir but not abacavir. Eight people (15%) dropped out of the abacavir group, compared with 3 (6%) from the tenofovir group. Three people (6%) discontinued abacavir because of hypersensitivity reactions, while only 1 (2%) stopped tenofovir because of side effects.

Median total cholesterol fell 0.2 mmol/L with tenofovir but stayed the same with abacavir (P = .016). Elevated low-density lipoprotein cholesterol levels eased 0.1 mmol/L with tenofovir but did not change in the abacavir group (P = .043). Triglycerides dropped 0.17 mmol/L with tenofovir and not at all with abacavir (P = .031).

Nucleoside toxicity expert Dr. Andrew Carr from St. Vincent’s Hospital in Sydney, Australia, observed that the better lipid changes with tenofovir may reflect the higher proportion in that group who stopped stavudine vs zidovudine. Other work has linked stavudine with lipid abnormalities (Martin), but that possibility awaits ongoing analysis, Dr. Moyle replied.

An earlier comparison of tenofovir with stavudine in treatment-naive patients found a significantly greater drop in bone mineral density with tenofovir (Gallant) In this trial, 19% of enrollees started the study with osteopenia. After 48 weeks, 27% taking tenofovir and 16% taking abacavir had osteopenia, but that difference lacked statistical significance.

Nearly everyone in both the tenofovir and abacavir groups maintained a viral load below 50 copies/mL throughout the study. After 48 weeks, the groups did not differ in markers of kidney dysfunction, another possible tenofovir-related side effect.

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