9th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 19-21 July 2007, Sydney, Australia

THE RISK OF DEVELOPING NRTI-INDUCED PERIPHERAL NEUROPATHY DECREASES OVER TIME: EVIDENCE FOR SPECIAL SUSCEPTIBILITY FROM THE DELTA TRIAL

Antiviral Therapy 2007; 12(Suppl. 2):L24 (abstract no. P-04)

A Arenas-Pinto¹, K Bhaskaran², D Dunn² and I Weller^1
1Centre for Sexual Health & HIV Research, University College London, UK; ²Clinical Trials Unit, Medical Research Council, London, UK

OBJECTIVES: Peripheral neuropathy (PN) is a common complication in HIV-infected individuals and is thought to be due to a toxic effect on mitochondria induced by nucleoside reverse transcriptase inhibitors (NRTI). This study was designed to assess the effect of cumulative NRTI exposure on the incidence of PN in patients included in Delta trial.

METHODS: A time-to-event analysis was performed using data from the Delta trial where HIV-infected individuals were randomized to receive zidovudine (AZT) alone or in combination with either didanosine (ddI) or zalcitabine (ddC). A flexible parametric survival model based on Royston and Parmar method was used to estimate the effect of duration of NRTI. A likelihood ratio test was used to assess whether this model was a better fit than the nested Weibull model in which the hazard function is monotonic or constant.

RESULTS: A total of 3,195 patients enrolled in Delta (1 and 2) trials were included in this sub-analysis. In a time-toevent analysis, the proportion of individuals that had experienced PN by 1 year from randomization was 3.0%, 2.9% and 8.2% in the AZT, AZT/ddI and AZT/ddC arms, respectively. The hazard of PN peaked over the first year following randomization. Compared with baseline, the estimated hazard of PN increased by 76% over the first 24 weeks, and then dropped. At 1 year, the risk was 32% higher than the baseline. There was strong evidence that this increase and decrease in the hazard of PN was a better fit to the data than a simpler model (P=0.0005 compared to a Weibull model).

CONCLUSION: Our results may support the hypothesis of a special susceptibility in a particular group of patients. Patients who are likely to develop PN when exposed to ddC tended to do so after a short exposure to the drug.

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2007-07-24
P-04

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