GW695634 is a non-nucleoside reverse transcriptase inhibitor (NNRTI) under development by GlaxoSmithKline. It may be active against HIV that has already developed resistance to the other NNRTIs, such as efavirenz (Sustiva) or nevirapine (Viramune). GW695634 is broken down in the body to produce GW8248.

NNRTIs work by blocking the activity of the reverse transcriptase enzyme. For more information on how NNRTIs work, see Reverse transcriptase inhibitors in Anti-HIV therapy: Ways of attacking HIV. For information on resistance to NNRTIs, see Resistance to non-nucleoside reverse transcriptase inhibitors in Anti-HIV therapy: Resistance.

A small 'proof-of-concept' study has shown that GW695634 can reduce viral loads in patients with NNRTI resistance. Forty-six patients were randomised to receive placebo or one of four doses of GW695634: 100, 200, 300 or 400mg twice daily. Fifty-five per cent of the patients had the K103N mutation and 30% had the Y181I/C, both of which confer resistance to all currently available NNRTIs.

At the start of the study, 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. After seven days' treatment, the patients receiving GW695634 had viral load reductions of between 1.1 and 1.6 log₁₀, compared with a median increase of 0.14 log₁₀ in the placebo group. The commonest side-effects were mild to moderate diarrhoea, nausea and rash (Becker 2005).

Reference

Becker S et al. Antiviral activity and safety of GW695634, a novel next generation NNRTI in NNRTI-resistant HIV-1 infected patients. Third International AIDS Society Conference on HIV Pathogenesis and Treatment, Rio de Janeiro, abstract WePe6.2C03, 2005.