AEGiS-14IAC: Pharmacodynamic effects of zidovudine 600 mg once daily versus zidovudine 300 mg twice daily in therapy-naïve HIV-infected patients (COD20002).

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Pharmacodynamic effects of zidovudine 600 mg once daily versus zidovudine 300 mg twice daily in therapy-naïve HIV-infected patients (COD20002).

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. LbPeB9020)

Ruane P, Richmond G, DeJesus E, Hill-Zabala C, Danehower S, Liao Q, Johnson J, Shaefer M
Tower ID Medical Associates, Los Angeles, United States

BACKGROUND: Recent intracellular zidovudine (ZDV) triphosphate data suggest that ZDV may be dosed once daily (QD). This 14-day pharmacodynamic study compared the virologic activity of ZDV monotherapy administered as 600mg QD v. 300mg BID.

METHODS: Antiretroviral-naïve subjects (≥18 years, HIV RNA ≥7,500 c/mL, CD4 ≥300 cells/mm³, no thymidine analog mutations) were randomized to open-label monotherapy with ZDV 600mg Q24H (±3 hours) or 300mg Q12H (±3 hours). HIV-1 RNA (VL) was measured daily and 1 dose of ZDV was observed each day. The sample size of 16 subjects/arm provided at least 80% power to detect a 0.036 difference in the slope of VL decline between groups over 14 days (approximately a 0.5 log₁₀ difference at Day 14). VL was log transformed prior to analysis.

RESULTS: All 32 subjects (94% male, median age 34 years) completed the 14-day study. Mean baseline (BL) VL was 4.33 and 4.40 log₁₀ c/mL in the QD and BID arms, respectively. The slope of VL decline from Days 1-14 was -0.045 for QD and -0.065 for BID (difference= -0.020 log₁₀ c/mL/day (p=0.065)). In additional analyses, the differences in slope of VL decline from Days 3-14, Days 1-10, and Days 3-10 were -0.009 (p=0.355), -0.036 (p=0.006), -0.024 (p=0.042), respectively, in favor of the BID arm. The mean change from BL (95% CI) in VL at Day 14 was -0.585 (-0.728, -0.442) and -0.849 (-1.067, -0.630) log₁₀ c/mL in the QD and BID arms, respectively (p=0.056). A faster initial decline in VL was observed in the BID arm compared to the QD arm; both arms achieved a mean reduction in VL of >0.5 log₁₀ c/mL. Both dosing regimens were well tolerated and safety profiles were comparable. No serious adverse events (SAE) or Grade 3/4 AEs were reported.

CONCLUSION: This study provides evidence that ZDV administered QD has antiviral activity as monotherapy, but further larger studies of ZDV 600mg QD as part of combination regimens are required to assess this dosing regimen in the clinical setting.

Keywords: AEGIS, Zidovudine, Lamivudine, Dideoxynucleosides, HIV Infections, HIV Seropositivity, Thymidine, abacavir, Male, Human

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LbPeB9020