HIV research highlights conference on infections

A new protease inhibitor for pediatric therapy, drugs for resistant HIV strains, and combination therapy aimed at reduced drug regimens were announced at the 6th Conference on Retroviruses and Opportunistic Infections held in February in Chicago.

Phase III trials of the protease inhibitor Agen erase (amprenavir) combined with two nucleoside reverse transcriptase inhibitors (NRTIs) reduced viral load to below 400 copies in 15 of 37 pediatric patients at eight weeks, according to research presented by manufacturer Glaxo Wellcome. The drug has been formulated as a twice daily dosage, and proved equally successful when given in 50 mg tablets or as an oral solution. If approved for marketing, the protease inhibitor would join two others approved for children now on the market. Side effects from trials included nausea, diarrhea, rash, oral paresthesia, and headache.

Preliminary NNRTI results presented

Glaxo also submitted research on the drug’s preliminary ability to reduce HIV levels in seminal fluid when taken as a monotherapy or in combination with NRTIs, findings the company will pursue in terms of anti-resistance therapy and transmission prevention.

Also submitted at the conference were preliminary study results on a pair of investigational non-nucleoside reverse transcriptase inhibitors (NNRTIs) and their activity against strains of HIV proving resistant to NNRTI therapy, presented by DuPont Pharmaceuticals.

Activity has been found in vitro when compared to existing NNRTIs, according to DuPont, when tested against five mutated viruses. Simian research has shown a half-life of the drug of between 20 and 76 hours at a 2 mg/kg dose, making researchers hopeful that a once daily dose could be produced as human trials are pursued.

And finally, GCI Healthcare/Roxane presented research it says shows that therapy using nucleoside analogues, specifically ddI and d4T, as a base treatment, then combined with either an NNRTI, 3TC, or protease inhibitor as the third combination element, produce equally effective treatment results in terms of plasma loads.

The company pursued the research to show that its NNRTI Viramune (nevirapine), already on the market, could be a successful substitute for protease inhibitors in terms of decreasing the number of drugs needed in a therapeutic regimen.

The study included the protease inhibitor indinavir, which, when taken as part of the combination therapy described above, totals 12 pills three times a day. By substituting the NNRTI, the regimen fell to eight pills twice daily, according to the submitted research. Comparable plasma loads were detected during randomized trials of 298 patients.