Final Results of CAESAR Study Demonstrate a Survival Benefit With 3TC

Dr.David Cooper from St. Vincent's Hospital in Sydney, Australia presented the final results of the multicenter study called CAESAR (conducted in Canada, Australia, Europe and South Africa) at the 4th National Conference on Retroviruses and Opportunistic Infections in Washington D.C. The objective of the study which enrolled 1892 HIV positive patients with CD4 counts between 25 and 250, was to assess whether the addition of 3TC with or without loviride, a new nonnucleoside reverse transcriptase inhibitor, to AZT containing regimens (AZT, AZT + ddI or AZT+ ddC) delayed HIV disease progression and improved survival. Patients enrolled were either antiretroviral naive (14-16%) or experienced (85%) and were randomly assigned in a 1:2:1 fashion to placebo, 3TC or the combination of 3TC and loviride. After one year open label administration of both drugs was offered. The average CD4 count ranged form 121-123 among the three arms. Sixty one percent of the patients were on AZT monotherapy at entry. More than half of the patients completed the trial (52%) without reaching a study endpoint (disease progression or death). After a median follow-up of 27-29 months the rates of new AIDS defining events were 55% lower for those on the 3TC arms than those on placebo and those on 3TC had a 58% reduction in mortality, even after adjusting for baseline characteristics. The reduction in disease progression was greater for the antiretroviral naive patients. There was no difference between the 3TC and 3TC and loviride arms, yet a subset analysis showed a strong trend favoring the 3TC + loviride arm for those who had baseline CD4 counts between 175-250 (rates = 3% and 6% for 3TC + loviride and 3TC, respectively). There were no differences in the rates of Grade 3 or 4 toxicities among the three arms; most of the toxicities were hematological (anemia). The authors concluded that adding 3TC to AZT or AZT + ddI or AZT + ddC significantly improved survival and delayed disease progression, although the additional benefit of loviride was not proven.