IAS: Low Dose of Nevirapine OK for HIV/TB

SYDNEY, July 24 -- In patients who have both HIV and tuberculosis, doctors can use a relatively low dose of nevirapine (Viramune) in combination with rifampin (Rifadin), researchers said here.

In a randomized clinical trial in Thailand, nevirapine at 400 milligrams a day worked as well as 600 milligrams in controlling HIV, according to Anchalee Avihingsanon, M.D., of the Thai Red Cross AIDS Research Center in Bangkok.

Despite rifampin's known interaction with nevirapine -- reducing serum levels by 20% to 50% -- the higher dose isn't needed, Dr. Avihingsanon told attendees at the International AIDS Society meeting.

In fact, she said, the study's data monitoring committee halted the trial early, arguing that the results were so clear there was no need to continue investigating the question.

The usual choice for people with both HIV and TB is a regimen based on efavirenz (Sustiva), she said. But doctors often turn to nevirapine when efavirenz is ruled out -- by allergy, pregnancy, or the simple unavailability of the drug.

But it has not been clear whether the nevirapine dose needs to be increased to counter the drug interaction with rifampin, Dr. Avihingsanon said.

To try to settle the question, she and her colleagues enrolled 32 patients who had both active TB and HIV and whose CD4 cell counts were less than 200 cells per microliter.

They were randomized to get either a low dose of 400 milligrams of nevirapine a day (in two doses) or a high dose of 600 milligrams administered once a day.

The researchers planned to treat the patients for 48 weeks, but the study was halted when a 24-week interim analysis showed essentially no difference in control of the HIV, she said.

At 24 weeks:

• On an intention-to-treat basis, the proportion of patients with HIV RNA less than 50 copies per milliliter was 62% in the high-dose arm and 50% in the low-dose arm, which was not significantly different.
• The median increase in CD4 cell count was 106 in the high-dose arm and 44 in the low-dose arm, which again was not significantly different.

On the other hand, she said, 25% of patients in the high-dose arm displayed nevirapine hypersensitivity and had to stop taking the drug, compared with only 6% in the low-dose arm.

There may be a lower limit to low-dose nevirapine, though. The study design included a two-week lead-in period, in which patients in the low-dose arm were given 200 milligrams a day of nevirapine and those in the high-dose arm received 400 milligrams, given in two doses.

During that period, Dr. Avihingsanon said, suboptimal nevirapine levels were seen in patients in the low-dose arm, suggesting that a 200-milligram dose should not be used.

The "encouraging" finding implies that lower doses of nevirapine don't predict poor clinical outcomes in this situation, said Gerald Friedland, M.D., of Yale University, who chaired the session.

"Lower doses are probably okay and higher doses are associated with more side effects and toxicity," Dr. Friedland said.

Whether the finding can be generalized to other populations -- especially physically larger Caucasians -- remains unclear, he said.