Factors influencing outcome of treatment with zidovudine of patients with AIDS in Australia

Abstract

In a multicentre study of zidovudine therapy in Australia commencing in June 1987, 308 homosexual or bisexual men with AIDS started on zidovudine by 30 June 1988. Using follow-up data collected through 31 December 1988, the outcome of the first 18 months of zidovudine therapy in these patients has been analysed in terms of efficacy, expressed as survival and as time to development of a new AIDS-defining condition, and in terms of safety, expressed as toxicity. Median survival from time of diagnosis of AIDS was 124 weeks, significantly longer (P < 0.001, logrank statistic) than the median survival of 44 weeks in historical controls representing AIDS patients prior to the availability of zidovudine therapy. Median survival time from starting zidovudine has not been reached in these patients, while 172 (56%) developed new AIDS-defining conditions, with median time to progression of 48 weeks. Anaemia requiring transfusion was experienced by 155 patients (50%). Significant differences (P < 0.01, logrank statistic) in survival were found in favour of patients who commenced zidovudine therapy (Dx-zidovudine time) within 12 weeks of diagnosis and had baseline Karnofsky scores ≥ 80, haemoglobin ≥ 11 g/dl, CD4+ cell counts ≥50 x 10⁶/l. Therapy-related significant differences (P < 0.01, logrank statistic) in survival were found in favour of patients with no weight loss and who received the full zidovudine dose (1.2g) during the first 52 weeks of therapy. Logistic regression analysis showed that the ability to tolerate full-dose zidovudine was best predicted by a baseline CD4+ cell counts ≥50 x 10⁶/l. In the proportional hazards model of survival, CD4+ cell counts ≥50 x 10⁶/l, Dx-zidovudine times ≤12 weeks and haemoglobin ≥11 g/dl were independently associated with improved survival. This study provides additional evidence that zidovudine is of benefit to patients with advanced HIV infection and documents that long-term therapy provides continuing benefits to these patients in terms of improved survival and increased time to disease progression. Despite the toxicity associated with this therapy, zidovudine provides a risk:benefit ratio advantageous to AIDS patients, particularly for those who commence zidovudine within 12 weeks of diagnosis and whose CD4+ cell counts are >50 x 10⁶/l.