HIV Digest	HIV Digest Archive

For years, multiple HIV treatment guidelines have agreed with the well-supported approach of a dual-nucleoside backbone with either efavirenz (EFV, Sustiva, Stocrin) or a boosted protease inhibitor. But specifically which dual-nucleoside/nucleotide reverse transcriptase inhibitor [NRTI] backbone should be selected has been the focus of numerous, important studies over the last few years. In the past year, the toxicity associated with a few years' use of stavudine (d4T, Zerit) has led to a decline in support for selecting this drug in initial regimens, given the data that supports the contention that there are more effective options.

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Another battleground of the NRTIs remaining in "preferred" lists has been the contrast between zidovudine (AZT, Retrovir) and tenofovir (TDF, Viread). A recent study allows a judgment of the outcomes when these two drugs are compared in a large, randomized study.

In this study, 517 patients were randomized to receive either tenofovir plus emtricitabine (FTC, Emtriva) or the coformulated tablet of zidovudine/lamivudine (AZT/3TC, Combivir). Both arms were taken in combination with efavirenz. By week 24, 11% of the patients had discontinued the tenofovir arm, while 21% on the zidovudine arm had stopped. Withdrawals due to adverse events was the main difference observed in these two arms. As a result, by intent-to-treat analyses, there was a superior outcome for the tenofovir arm, with 87% of the patients (compared to 78% on the zidovudine arm) achieving suppression to <400 copies (P = .01) and a 95% confidence interval that shows superiority of the tenofovir arm. By a 50-copy cutoff, the arms had a 73% vs. 65% response on the tenofovir and zidovudine arms, respectively. There was also a superior CD4+ response to tenofovir, with an increase of 129 cells, vs. 111 cells on the zidovudine arm. Resistance outcomes were similar in these arms.

The adverse event of anemia was further defined for patients who withdrew from the trial due to this outcome: A striking drop in the hematocrit from a mean of 40 at baseline to 22 was documented at the time of discontinuation-- changes that are clinically meaningful. There were no reported changes in serum creatinine on the tenofovir arm, and two reported increases in creatinine on the zidovudine arm. This study will present powerful data to both clinicians who are considering initiation of therapy for their patients and for patients deciding upon their first regimen: On every measurement presented, the arm containing tenofovir was superior for safety, as well as for immunologic outcomes.