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DAPD in 18 Treatment Experienced Patients
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"Preliminary Results of Dosing of Amdoxovir in Treatment-Experienced Patients"
At the recent Retrovirus Conference, researchers reported the most study results on DAPD (also called Amdoxovir), which is a nuke that had shown effectiveness against nuke resistance. This is a small study in 18 treatment-experienced patients which examines opthalmalogic findings in patients on DAPD combined with a background regimen optimized by the investigator.
DPAD-150 is a randomized, open-label, phase 1/2 study looking at different doses of DAPD. In vitro studies showed DAPD has activity against HIV strains resistant to AZT/3Tc and d4T/3TC. In HIV-infected patients with nuke resistance, DAPD has shown effectiveness. DAPD-150 is an ongoing 96-week study evaluating DAPD doses of 300 mg twice daily and 500 mg twice daily. 18 treatment-experienced patients who failed prior AZT/3TC or d4T/3Tc therapy received either of the two DAPD doses. Upon study entry, CD4 counts had to be above 50 cells/mm3 and HIV RNA between 5000 and 250,000 copies/ml. Most patients in the study were white men, average age 40, HIV viral load 25,000 copies/ml, CD4 count 326.
The 18 patients were a very experienced group: median number of previous HIV drugs=10 (range 4-16); median duration of previous therapy=7.7 years (range 2-14), median number of NRTIs=3 (range 0-8), median exposure to DAPD=117 days.
Baseline opthalmalogic exams were not performed. Study analysis consists of safety assessment, and CD4 and viral load changes at week 12.
RESULTS
11 of 18 patients discontinued: 5 due to opthalmalogic problems (lens opacities that did not effect visual acuity); 4 due to virologic failure; and 2 who withdrew or were non-adherent. There were no deaths, serious adverse events, 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 1 patient in each dose group.
Some of the opthalmalogic (slit lamp) findings described were: midposterior subcapsular cataracts at day 25 in 1 patient at the 500 mg DAPD dose who was 52 years old with a family history, and tobacco use; minor opacities at day 54 and slight lens opacities at day 90 on DAPD for a patient on the 500 mg dose who is 38 yrs old, uses tobacco and alcohol; no abnormalities at day 44, slight lens abnormalities (peripheral pinpoints) at day 105 on DAPD for a patient on 500 mg dose who is 49 yrs old with tobacco use; no abnormalities at day 42, slight lens abnormalities at day 104 on DAPD for a patient on the 300 mg dose who is 41 yrs old and experienced a transient drug-induced episode; no abnormalities at day 5, slight lens opacities (peripheral pinpoint) on day 48 for a patient on the 300 mg dose who has a family history.
After 12 weeks on DAPD average CD4 counts increased by 55 cells (n=11). Median viral load reduction at week 12 was -0.90 log (n=11): -1.53 log for patients taking 300 mg dose and -0.75 log for patients taking 500 mg dose. 7 patients (58%) had 0.5 log decline in viral load at week 12. 5 patients (42%) had a 1.0 log decline at week 12. Researchers reported no signs or symptoms related to renal disorders or hyperglycemia, and concluded that DAPD and optimized ART background achieved >0.5 log decrease in about 40% of patients, was well tolerated, and ongoing patients remain on DAPD.
Abst. 554. M. Thompson (Atlanta, GA) et al. Retrovirus Conference.
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