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Triple Nucleoside Regimen of Abacavir, Stavudine and Didanosine Is Neither Effective Nor Well Tolerated for Treating HIV Infection

The triple nucleoside reverse transcriptase regimen of abacavir, stavudine and didanosine is neither effective nor well tolerated and therefore should not be recommended for the treatment of naïve HIV patients, indicate findings of a randomised controlled trial.

The regimen had been compared with ritonavir and saquinavir and with nelfinavir and nevirapine, in combination with lamivudine and zidovudine, reported Dr Jan Gerstoft, in the Department of Infectious Diseases at Rigshospitalet, in Copenhagen, Denmark, and colleagues.

The trial included 180 antiretroviral drug-naive HIV-infected patients, who at baseline had a median CD4 cell count of 161 million per litre (range 0 to 920 million per litre). Their baseline median viral load was 5.0 log10 copies of HIV RNA per millilitre (range, 2.7 to 6.7 log 10), the researchers noted.

At 48 weeks, only 43% of patients in the abacavir, stavudine and didanosine arm had 20 or fewer copies of HIV RNA per millilitre, compared with 69% in the nelfinavir and nevirapine arm and 62% in the ritonavir and saquinavir arm. The abacavir, stavudine and didanosine arm had a particularly poor outcome in patients with higher viral load and AIDS at baseline.

In a multivariate analysis, at 48 weeks, patients in the abacavir, stavudine and didanosine arm had an odds ratio of obtaining a viral load of 20 or fewer HIV RNA copies per millilitre of 0.25 versus nelfinavir and nevirapine, and an odds ratio of 0.53 versus ritonavir and saquinavir, the investigators reported.

Adverse events were more frequent in the abacavir, stavudine and didanosine arm, where 27% of the patients experienced neuropathy, 12% had suspicion of hypersensitivity, and 8%, had an increase in lactate accompanied by systemic symptoms. Almost two thirds of the patients in the abacavir, stavudine and didanosine arm discontinued therapy.

"The side effects were substantial in the A/S/D [abacavir, stavudine and didanosine] arm," the authors wrote. "Nearly all of the adverse effects in the arm could be related to what is considered mitochondrial toxicity, with neuropathy and elevated lactate being most prominent."

"In summary," the authors concluded, "the evaluated triple NRTI regimen carried many side effects and had a low efficacy. It cannot be recommended for use in drug-naïve patients."

AIDS 2003 Sep 26;17:14:2045-2052. "Low efficacy and high frequency of adverse events in a randomized trial of the triple nucleoside regimen abacavir, stavudine and didanosine"

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