IAS: ‘Next generation’ NNRTI GW695634 is safe and active in NNRTI-resistant patients

The new non-nucleoside reverse transcriptase inhibitor (NNRTI) GW695634 causes significant viral load reductions when given to HIV-infected patients with NNRTI-resistant virus, according to a poster presentation at this week’s Third International AIDS Society Conference in Rio de Janeiro.

Although similar drugs have recently been withdrawn from development, this study shows that Glaxo SmithKline's GW695634 may eventually become a suitable option for patients who have developed resistance to the existing NNRTIs, nevirapine (Viramune) or efavirenz (Sustiva). Currently, failure of one of these two drugs leads to resistance to both members of the class.

Forty-six HIV-positive patients with a median of two primary NNRTI resistance mutations were randomised to receive placebo or one of four doses of GW695634: 100, 200, 300 or 400mg twice daily. Neither the patients nor the investigators knew which dose each patient was taking. Fifty-five per cent of the patients had the K103N mutation, and 30% the Y181I/C mutation, both of which confer resistance to all currently available NNRTIs.

At baseline, the five groups of patients had median CD4 cell counts between 230 and 345 cells/mm³ and viral loads between 25,100 and 39,800 copies/ml. However, after seven days’ therapy, the patients receiving GW695634 achieved median viral load reductions of between 1.1 and 1.6 log₁₀. In contrast, those receiving placebo had a median increase of 0.14 log₁₀ (p

The most frequent side-effects seen in the drug groups were diarrhoea, nausea and rash. These were of mid or moderate severity.

“These data provide a ‘proof-of-concept’ which supports further clinical development of GW695634 for use in subjects failing currently marketed NNRTI medications,” the investigators conclude.