Background: Amdoxovir (DAPD), a dioxalane guanosine analog, and its deaminated metabolite DXG are nucleoside reverse transcriptase inhibitors (NRTIs). DAPD 150 is a 96-week study designed to evaluate the long-term safety, tolerability, and antiviral activity of DAPD.

Methods: In an on-going nonrandomized, open-label, Phase I/II study, a total of 18 HIV-infected, treatment-experienced subjects were randomized to receive either 300 mg BID or 500 mg BID DAPD in addition to their background regimen that could be optimized at the discretion of the investigator.

Results: Subjects were treatment experienced with a median duration of 8 years of exposure to a median of 10 ART drugs and with a median of 5 NRTI mutations. The median duration of treatment in patients (pts) receiving at least one dose of DAPD is 16.8 weeks. The table below shows the preliminary results at week 12 of the study. DAPD was well tolerated across both dose groups. There were no deaths, SAEs, or dose-related trends in adverse events. No serum creatinine or glucose elevations above grade 1 or abnormal urinalysis results were reported. There were no treatment-emergent Grade 3 or 4 laboratory toxicities except for triglycerides in one pt in each dose group. Ten pts discontinued the study: 2 due to VF, 3 for non-compliance with the protocol, and 5 for presence of lens opacities which did not impact visual acuity.

Conclusions: Preliminary results suggest antiviral activity and tolerability of DAPD in treatment-experienced subjects and warrant further studies.

Baseline CD4	338 (n = 17)
Median change from baseline at week 12	55 (n = 11)
Baseline HIV RNA	4.41 (n = 17)
Median change from baseline at week 12	-0.90 (n = 11)
Number of patients at week 12 with 0.5 log drop from baseline	7 (58%)
1.0 log drop from baseline	5 (42%)