14th International AIDS Conference Barcelona, Spain — July 7-12, 2002

Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. LbPeB9014

BACKGROUND: A multinational, randomized, double-blind, placebo-controlled study evaluated the antiviral activity, safety and tolerability of once-daily d4T extended/prolonged release capsules (XR/PRC) compared to the current twice-daily formulation of d4T immediate release (IR), when used in a HAART regimen in treatment naïve HIV-infected subjects.

METHODS: Adult subjects with CD4 ≥100 cells/μL(c/μL) (≥75 c/μL if no prior AIDS event) and HIV RNA ≥ 2,000 copies/mL (c/mL) were randomized to either d4T XR/PRC or d4T IR, each in combination with 3TC + EFV. The study had 90% power to demonstrate non-inferiority based on the primary outcome of proportion with HIV RNA < 400 c/mL at 48 weeks (wks).

RESULTS: Of 797 randomized subjects, 783 began treatment. Median baseline HIV RNA and CD4 were 4.8 log₁₀ c/mL and 277 c/μL, respectively. All subjects had 48 wks of follow-up (median 56 wks). Two virologic response (VR) analyses for LOQ <400 c/mL demonstrate similarity: VR-Treated (VR-T, an ITT analysis for all treated subjects), XR/PRC 80% vs IR 75% ([XR-IR], -4.4, 95%CI -1.5, 10.3); VR-Completers (VR-C), 91% XR/PRC vs 89% IR. Analyses for LOQ <50 c/mL also support similarity: VR-T, XR/PRC 59% vs IR 57%; VR-C, XR/PRC 67% vs IR 67%. Mean increases in CD4 were: XR/PRC +187 vs IR +181 c/μL. At 48 wks, 4% of subjects discontinued therapy in each group due to an adverse event (AE). Grade 3/4 clinical AEs occurred in 43 (11%) of XR/PRC and 41 (10%) of IR subjects. Events of hepatotoxicity, pancreatitis, or symptomatic hyperlactatemia/lactic acidosis syndrome occurred in a total of 3 (<1%) XR/PRC vs 7 (1.5%) IR subjects. Grade 2-4 peripheral neurologic symptoms related to therapy occurred in 3% of XR/PRC and 5% of IR subjects.

CONCLUSIONS: d4T XR/PRC is well tolerated and exhibits an antiviral and immunologic profile similar to that of d4T IR when used in a HAART regimen for treatment-naïve patients. d4T XR/PRC is an option when designing once daily regimens.

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1Clinique du Quartier Latin, Montreal, Canada.

2Univ of CA, Davis Med Ctr. Sacramento, CA.

3Hopital de L'Hotel Dieu, Nantes, France.

4Pharmaceutical Research Institute, Bristol-Myers Squibb, Wallingford, CT.

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