AEGiS-15CROI [37]: Efficacy and Safety of Once-daily Atazanavir/Ritonavir Compared to Twice-daily Lopinavir/Ritonavir, Each in Combination with Tenofovir and Emtricitabinein ARV-naive HIV-1-infected Subjects: The CASTLE Study, 48-week Results

15th Conference on Retroviruses and Opportunistic Infections

Boston, Massachusetts - February 3-6, 2008

EFFICACY AND SAFETY OF ONCE-DAILY ATAZANAVIR/RITONAVIR COMPARED TO TWICE-DAILY LOPINAVIR/RITONAVIR, EACH IN COMBINATION WITH TENOFOVIR AND EMTRICITABINEIN ARV-NAIVE HIV-1-INFECTED SUBJECTS: THE CASTLE STUDY, 48-WEEK RESULTS

Conf Retrovir Opportunistic Infect 2008 Feb 3-6;15: (abstract no. 37)

Jean-Michel Molina¹, J Andrade-Villanueva², J Echevarria³, P Chetchotisakd⁴, J Corral⁵, N David⁶, M Mancini⁷, L Percival⁷, A Thiry⁷, and D McGrath⁷
¹Hosp St Louis, Paris, France; ²Hosp Civil de Guadalajara, Mexico; ³Hosp Natl Cayetano Heredia, Lima, Peru; ⁴Khonkaen Univ, Thailand; ⁵Hosp Intl Gral de Agudos Oscar Alende, Buenos Aires, Argentina; ⁶Brooklyn Med Ctr, Western Cape, South Africa; and ⁷Bristol-Myers Squibb R&D, Wallingford, CT, US

BACKGROUND: Atazamavor/ritonavir (ATV/r) is as effective as lopinavir (LPV)/r with more favorable lipid and gastrointestinal profiles in treatment-experienced HIV-infected patients. Comparative data in ARV-naive patients are needed.

METHODS: CASTLE is a randomized, open-label, multicenter, ongoing 96-week study to assess non-inferiority (10% margin) of ATV/r 300 mg/100 mg once-daily vs LPV/r 400 mg/100 mg twice-daily, both in combination with fixed-dose tenofovir (TDF) 300 mg/emtricitabine (FTC) 200 mg once-daily, in treatment-naïve patients. The primary end-point was the proportion of patients with HIV RNA<50 copies/mL at week 48; planned secondary assessments included percent with HIV RNA <400 copies/mL, CD4 cell count change, and safety.

RESULTS: Of the 883 patients we randomized, 878 were treated. Baseline demographics and characteristics were well balanced. Median CD4 205 cells/mm³; median plasma HIV RNA 4.98 log10 copies/mL. At week 48, mean CD4 increases from baseline for ATV/r and LPV/r were 203 and 219 cells/mm³, respectively. Fewer patients on ATV/r (2%) than LPV/r (8%) initiated lipid-lowering therapy. The proportion of patients with a total cholesterol (TC):HDL ratio >5 at week 48 was 12% and 20% on ATV/r and LPV/r, respectively. Patients on ATV/r had a lower incidence of grade 2-4 treatment-related diarrhea (2% vs 11%) and nausea (4% vs 8%) than LPV/r. Grade 3-4 alanine aminotransferase/aspartate aminotransferase (ALT/AST) elevations were low (≤2%) on both arms. Discontinuations prior to week 48 were: ATV/r, 9%; LPV/r, 13%. Adverse event-related discontinuations were 2% and 3% on ATV/r and LPV/r, respectively; 3 patients (<1%) discontinued ATV/r due to jaundice/hyperbilirubinemia.

CONCLUSIONS: In treatment-naive patients, ATV/r demonstrated similar efficacy, a lower incidence of gastrointestinal-related adverse events, and a significantly better lipid profile (TC, triglycerides, non-HDL) compared to LPV/r. In combination with TDF and FTC, both ATV/r and LPV/r were well tolerated with few discontinuations through 48 weeks.

	ATV/r	LPV/r	Difference Estimate (95%CI) (ATV/r – LPV/r)
CVR^a	n = 440	n = 443
% <50 copies/mL	78	76	1.7 (–3.8 to 7.1)
% <400 copies/mL	86	82	3.3 (–1.5 to 8.1)
CVR^a, Baseline CD4 < 50 cells/mm³	n= 58	n= 48
% <50 copies/mL	78	63
Fasting Lipid Mean % D from baseline at 48 weeks^b	n= 421	n= 415
Total-C (TC)	12	24	–9.5 (–11.8 to –7.0)^c
LDL	12	15	–2.9 (–7.1 to 1.5)
HDL	27	32	–3.8 (–7.8 to 0.3)
Non-HDL	7	21	–11.6 (–14.5 to –8.7)^c
TG	13	51	–25.2 (–29.8 to –20.2)^c
^a Confirmed Virologic Response (ITT), Non-Completers = Failure ^b Last Observation Carried Forward ^c p < 0.0001

Download abstract

2008-02-03
37

Copyright © 2008 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health.