Halving the dose of Zerit (stavudine) may reduce the risk of serious side effects without compromising its efficacy, say researchers of a study published in the April 15 issue of Clinical Infectious Diseases.

Bristol-Myers Squibb’s nucleoside reverse transcriptase inhibitor (NRTI) Zerit has fallen out of favor in many parts of the world because of its side effects, including lipoatrophy, increases in lipid levels, a dangerous buildup in the blood of lactic acid (lactatemia), and an increased diabetes risk. Many of these side effects likely occur because Zerit can damage the mitochondria that help keep cells functioning properly.

In the U.S. and other industrialized nations, NRTI options are plentiful and people can avoid Zerit altogether. But the lower dose may help HIV-positive people who do need it, including those in developing countries where options are fewer and stavudine is affordable.

The study conducted by Grace McComsey, MD, of Case Western Research University in Cleveland, enrolled 24 HIV-positive patients who’d been on full-dose Zerit for at least six months and had signs of mitochondrial toxicity (e.g., lactatemia or lipodystrophy). Approximately half of the trial volunteers reduced their Zerit dose from the standard 40 mg to 20 mg twice daily, or from 30 mg to 15 mg for those weighing 132 pounds or less.

After 48 weeks, six of the 15 participants who’d switched to the reduced-dose Zerit had viral loads that became detectable, compared with only two of the nine participants who remained on the full dose.

In terms of side effects, the average level of fat mtDNA, a marker of mitochondrial health in fat cells, increased by 67 percent in the group who switched to the reduced Zerit doses, but remained the same in the group who stayed on full-dose Zerit. Lactate levels decreased by 0.27 mmol/L in the reduced-dose group, but did not improve in the full-dose group.

Modest improvements in body composition, including pre-study belly accumulation, were reported among those who switched to lower-dose Zerit compared with those who remained on the standard dose of the drug. Similarly,

bone mineral density, the loss of which can increase the risk of broken bones, decreased in the group that remained on full-dose Zerit, but remained stable in the reduced-dose group.

McComsey’s team acknowledges that the study is small and that side effect improvements were significantly less than those seen in other studies where participants switched from Zerit to another drug altogether. Given that so many people in the world rely on the availability of stavudine formulations, the authors conclude that the safety and efficacy of reduced dosing is encouraging.