Many doctors have long thought that Viramune was just as potent as Sustiva, but they didn't have good data to back them up. Now it appears that they do. Still, as usual doctors are disagreeing about the strengths of the two drugs.
"Did it [study results] tell us anything we didn't already know?" said one HIV specialist who believes both drugs are equally effective. Yet another said that Sustiva is still the drug to bet on for strength and durability. He noted that Sustiva may be safer than Viramune. It has also shown excellent results in many more large clinical tirals, including superiority over most of the protease inhibitors.
The international 2NN study was reported at the 10th Conference on Retroviruses and Opportunistic Infections (CROI) in February, held in Boston. Researchers found that efficacy in terms of viral load decrease and T-cell increase was "comparable" between Sustiva and Viramune. "NN" stands for non-nucleoside, the class of HIV drugs Viramune and Sustiva belong to.
The importance of 2NN is the strength of the science: it's a large study (1,216 participants). It was randomized (people were randomly put into the different arms of the study, which helps eliminate bias). Plus, it was a prospective study, which means that it was designed and then carried out. Several previous retrospective ("look-back") studies suggested that Sustiva was more effective than Viramune, but those studies are not as reliable as prospective clinical trials.
What else did 2NN show? Ironically, treatment failure was high -- 44% for Viramune twice daily and 38% for Sustiva. However, the study used a strict definition of failure (which is common in clinical trials): less than one log decline in viral load within three months; viral load failure after six months (two consecutive viral loads above 50); disease progression or change in therapy. One audience member thought that the two viral loads over 50 could "bias" the results, saying that, "In our experience, most people who go above 50 return to below 50."
Still, the rate of Grade 3 or 4 (serious) adverse events was high, more than 22 percent for every combination of drugs. However, the discontinuation rate for toxicity was the same for both drugs.
The only significant difference in the rate of side effects was a higher incidence of liver-associated laboratory abnormalities for Viramune, especially in the once-daily dose (13.2%). (Once-daily Viramune has not been approved by the U.S. Food and Drug Administration, or FDA.) But clinical hepatitis did not differ among the meds.
However, there were two deaths attributed to Viramune, both in residents of poor countries. One was related to Stevens-Johnson syndrome and the other to liver toxicity. A third death occurred due to Zerit. Each drug combination was given with Zerit and Epivir, which could be changed due to toxicity. Viramune was given at its FDA-approved dose of 200 mg (one tablet) twice a day, or the unapproved 400 mg once a day. Sustiva was probably given as three capsules once a day. (Today it is FDA-approved as one 600 mg tablet once a day.) A fourth combination, using Sustiva and Viramune along with Zerit and Epivir, had the highest rate of toxicity, and the researchers recommended that people not take the two non-nukes together.
Choosing between Viramune and Sustiva may have to do with side-effects and toxicity concerns. A person with a history of mental illness or illicit drug use may experience higher reates of psychiatric side effects from Sustiva. These include vivid dreams and sleep disturbances, and even flashbacks. Sustiva can also raise cholesterol and triglycerides more than Viramune, though protease inhibitors tend to have a greater effect on lipids than either Sustiva or Viramune.
Women may be between a rock and a hard place. They're more prone to serious rashes and liver toxicity with Viramune, both of which can be life threatening. On the other hand, Sustiva cannot be taken by someone who's hoping to become pregnant. It may cause birth defects.
The data from the 2NN trial are reassuring for people who may need to switch from one NNRTI to the other because of toxicity or side effects. There is previous evidence that this strategy works well. And finally, Viramune is cheaper by about $100 less a month. This might cause government medical assistance programs, such as ADAP (AIDS Drug Assistance Program), that are low on funds to push for Viramune prescriptions over Sustiva.