Third International Congress Drug Therapy in HIV Infection 3-7 November 1996 Glasgow, UK

CLINICAL AND SURVIVAL BENEFIT OF 3TC™ IN COMBINATION WITH ZIDOVUDINE-CONTAINING REGIMENS IN HIV-1 INFECTION: INTERIM RESULTS OF THE CAESAR STUDY

C.Katlama
Hôpital Pitié-Salpétriè, Paris on behalf of the CAESAR Co-ordinating Committee.

Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. SS2.1
AIDS 1996, Vol. 10 (Suppl. 2);S9

CAESAR was a randomised, double-blind, multicentre study comparing the efficacy and safety of 3TC or 3TC+loviride (LVR) versus placebo in HIV-1 infection. Patients with entry CD4 counts 25-250 cells/mm³, Karnofsky score ≥ 70, were randomised at 1:2:1 to add placebo, 3TC (150mg bid) or 3TC (150mg bid) + LVR (100 mg tid) to their concurrent therapy of AZT, AZT+ddI or AZT+ddC. The duration of blinded treatment was 52 weeks. The primary clinical end-point was progression to a new AIDS event or death.

1892 patients were randomised to treatment : Placebo 482, 3TC 935 and 3TC+LVR 475. Baseline characteristics were evenly balanced across the three treatment groups. 62% entered the study on AZT monotherapy, 26% had prior CDC stage C event, the median CD4 cell count was 131 cells/mm³ and the median follow-up duration was 52 weeks. Results from a preplanned interim analysis with data up to 5th July 1996, reviewed by the DSMB on the 15th July 1996, showed a 54% reduction in disease progression in the 3TC containing arms. Progression rates in the overall population were: Placebo 81/482 (17% ); 3TC 80/935 (9%); 3TC + LVR 38/475 (8%); HR=0.475, 95% CI 0.338-0.665, p<0.0001. Mortality was also significantly reduced in the 3TC arms compared to placebo : Placebo 22/482 (4.6%); 3TC 22/935 (2.4%); 3TC+LVR 13/ 475 (2.7% ), p= 0.012. Sub-group analysis of current treatment at baseline confirmed similar results. There was a 55% reduction in disease progression in the 3TC containing arms in patients entering the trial on AZT monotherapy as current treatment and a 49% reduction in those entering the study on combination therapy. Changes in CD4 cell counts and HIV-I RNA levels in a subset of 332 patients were consistent with the clinical results. The addition of 3TC and LVR did not result in additional clinical or laboratory toxicities to those seen in the control. We conclude that the addition of 3TC to concurrent AZT-containing regimens significantly reduced progression to AIDS or death and increased survival significantly. Additional clinical benefit was not shown with the addition of loviride to 3TC. However, as the trial was not powered to detect this, further investigations will be perfonned to assess the effect of loviride in certain sub-groups. CAESAR was formally terminated on July 23rd 1996 at the recommendation of the DSMB.

Presenting author: C.Katlama

1996-11-03
SS2.1

Originally published in AIDS Volume 10, Supplement 2 and hosted with permission of the publisher Lippincott Williams & Wilkins, 250 Waterloo Road, London, SE1 8RD, UK. Tel: +44 (0)20 7981 0700 Fax: +44 (0) 7981 0701

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