IAS: New Drugs Effective Against HIV Resistance

SYDNEY, July 25 -- A combination of two new HIV drugs can reduce the virus to undetectable levels even in patients with a highly resistant strain, according to two studies presented here.

In the DUET-1 and DUET-2 trials, researchers tested the new protease inhibitor darunavir (Prezista) against the combination of darunavir and emtravirine, a new non-nucleoside reverse transcriptase inhibitor (NNRTI). In both arms of the trials, low-dose ritonavir was also given.

The proportion of patients reaching an undetectable level of HIV -- defined as fewer than 50 copies of HIV RNA per milliliter of blood -- was 17% higher for patients on the combination in DUET-1 and 18% higher in DUET-2, investigators reported at the International AIDS Society meeting.

A typical patient in the two parallel studies had been treated with up to a dozen drugs, had suffered one or more AIDS-defining illnesses, and had a CD4 cell count of about 100 per microliter of blood.

"They were also harboring highly-resistant virus," said Christine Katlama, M.D., of the Hpital Piti-Salptrire in Paris, who presented the studies.

She noted that two-thirds of the patients had two or more mutations that caused resistance to NNRTIs and half had four or more mutations that generate resistance to protease inhibitors.

In both studies, patients were placed on the best possible background regimen of drugs. The all were treated with darunavir and half were randomly assigned to also get emtravirine.

By week 24 of treatment:

• In DUET-1, 56% of patients getting emtravirine and 39% of those in the other group had reached a confirmed viral load of less than 50 copies per milliliter. The difference was significant at P=0.005.
• In DUET-2, the corresponding proportions were 62% and 44%, significant at P=0.0003.

Interestingly, even when patients had no other active drugs in their background, more than 40% of patients getting both darunavir and emtravirine reached the less than 50-copy level.

Adverse effects were similar between the arms, she said, except for rash and diarrhea -- usually mild and self-limited -- which was higher in the emtravirine arm, Dr. Katlama said.

The drug will be useful to clinicians, because it represents a chance to use a member of the NNRTI class in patients who have developed resistance, said Jose Gatell, M.D., head of the infectious diseases and AIDS units of the University of Barcelona hospital. Dr. Gatell was co-chair of the 2002 World AIDS Conference in Barcelona.

Usually, when patients need salvage therapy, "we don't even think of the NNRTIs, because they will have usually developed resistance," he said. "Now we will have something (in that class) available to us that works."

Detailed reports on the 24-week data from the two studies were published earlier this month in a special HIV issue of The Lancet, somewhat to the chagrin of IAS officials, who had expected the journal to hold off publishing until the eve of this conference.