The Pharmaceutical Journal
Vol 269 No 7207 p90
20 July 2002

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JAMA (jama.ama-assn.org)

Two protease inhibitors better than one after failure of previous HIV treatment

Using two new protease inhibitors as part of a salvage regimen to treat HIV-infected patients whose previous regimen has failed is better than using one new protease inhibitor, say researchers (JAMA 2002;288:169).

Dr Scott Hammer, Columbia University College of Physicians and Surgeons, New York, and colleagues from the AIDS Clinical Trials Group conducted a randomised trial involving 481 patients to assess whether adding a second new protease inhibitor — saquinavir, indinavir or nelfinavir — would improve the antiretroviral efficacy of a four-class drug regimen.

Patients received open-label amprenavir, abacavir, efavirenz and adefovir dipivoxil and were randomised to receive a second new protease inhibitor or placebo.

The researchers found that adding a second protease inhibitor to the regimen decreased the HIV-1 RNA level to less than 200 copies/ml in 35 per cent of patients compared with 23 per cent of patients given placebo (P=0.002).

They also found that a subgroup of patients who were naive to non-nucleoside reverse transcriptase inhibitor (NNRTI) therapy had a higher rate of viral suppression compared with patients who had previously been treated with this class of drug (43 per cent vs 16 per cent, P<0.001). "This emphasises the importance of having at least one (preferably more) potent agent, against which little or no viral cross-resistance is likely to exist, to use as the cornerstone of a salvage regimen," say the researchers.

In addition, a lower susceptibility to the NNRTI efavirenz at the start of the study was associated with decreased viral suppression at 24 and 48 weeks.

Commenting on the study, Dr Joel Trachtenberg and Dr Merle Sande, University of Utah, Salt Lake City, say in an accompanying editorial that the effectiveness of the NNRTI class is impressive but warn that resistance to NNRTIs may be increasing, especially when the drugs are given in non-suppressive regimens or as single-dose prophylaxis (ibid p239).