AIDS 2008 Abstract - Safety profile of apricitabine, a novel NRTI, during 24-week dosing in experienced HIV-1 infected patients

Safety profile of apricitabine, a novel NRTI, during 24-week dosing in experienced HIV-1 infected patients

Presented by Susan Cox, Australia.

S. Cox¹, S. Moore¹, J. Southby¹, A. Alsumde²

¹Avexa Ltd, Melbourne, Australia, ²Avexa Ltd, San Francisco, United States

Background: Apricitabine (ATC) is a novel cytidine non-nucleoside reverse transcriptase inhibitor (NRTI) with activity in both treatment-naive and treatment-experienced HIV-1 infected patients, accompanied by a favourable safety profile. Pre-clinical data show a low propensity for mitochondrial, hepatic or bone marrow toxicity.
Methods: Safety data from a 24-week study of ATC (600mg and 800mg BID) or 3TC (150mg BID) in combination with other antiretroviral therapy (ART) in 51 treatment-experienced patients (with the M184V mutation) are available.
Results: There were no deaths, no serious adverse events and no discontinuations owing to related adverse events (AEs) in patients receiving ATC. AEs considered treatment-related were mild/moderate and were GI-related. There were no cases of rash, pancreatitis, hypersensitivity reaction, hyperlactaemia, hyperlipasaemia or LFT increases associated with ATC, and ATC had no effect on serum lipids or creatinine. The most common ART used together with ATC were tenofovir, abacavir, didanosine, lopinavir, atazanavir and ritonavir. Hyperbilirubinaemia occurred in patients taking atazanavir. The most common AEs were nausea, diarrhoea, nasopharyngitis, hypertriglyceridaemia and upper respiratory tract infection, which occurred equally between patients receiving ATC or 3TC.

Adverse event	600mg ATC (n=17)	800mg ATC (n=18)	150mg 3TC (n=16)
Nausea	2 (11.8%)	4 (22.2%)	3 (18.8%)
Diarrhoea	4 (23.5%)	6 (33.3%)	4 (25.0%)
Nasopharyngitis	3 (17.6%)	2 (11.1%)	2 (12.5%)
Hypertriglyceridaemia	2 (11.8%)	1 (5.6%)	3 (18.8%)
Upper respiratory tract infection	0	3 (16.7%)	2 (12.5%)

Conclusions: ATC is safe and very well tolerated over 24 weeks in combination with other ART. There was no evidence of peripheral neuropathy, myelotoxicity, hepatotoxicity, hypersensitivity, lipidaemia, hyperlipasaemia or renal toxicity. As a second-line drug for treatment-experienced patients, ATC provides antiviral activity with an unparalleled safety and tolerability profile.