Mitochondrial toxicity with AZT and d4T – and benefits of switch to abacavir

Simon Collins, HIV i-Base

Two-year follow up data from Australian patients randomised to switching AZT or d4T to abacavir in the MITOX study showed continued benefit, reported Andrew Carr. [20]

Serial DEXA and CT scans previously reported a mean increase of 0.39kg limb fat after 24-weeks compared to controls continuing on thymidine analogues. At this year’s meeting follow-up data also presented responses of the control group who switched to abacavir at week 24.

Mean follow-up was 102 weeks with 74/111 patients having imaging data at week 104. Limb fat in the patients who originally switched to abacavir had continued to increase to +1.26kg from a baseline of 3.7kg.

Although these changes may not show great clinical differences, it is very important that lipoatrophy has both stopped progressing and in a limited way also reversed – and that this is documented in measurable changes. It is not know whether the original fat loss had reached a plateau either due to maximal adipocyte depletion or before that level.

The control patients also reported similar improvement once they switch from AZT or d4T at 24 weeks.

Multivariate analysis showed greater increase in limb fat was associated with lower baseline bone mineral density (p=0.006), shorter duration of AZT pre-study (p=0.024) and shorter duration of d4T on study (p=0.004).

Raghavan and colleagues found small but statistically significant differences in the rate of change in BMI, body cell mass, total body fat and circumferences and skin folds between patients using ddI/d4t compared to those using abacavir/3TC in both peripheral and central sites. [21]

BIA and anthropometric measurements (skin-fold and body circumference) were taken every four months over a median of 33 months follow up in 96 patients on their first combination enrolled in a substudy of CPCRA 058.

This article is part of a longer report from the 5th International Workshop on Adverse Drug Reactions and Lipodystrophy, 8-11 July 2003, Paris. Part eight of this report.


Unless otherwise stated, all abstracts refer to the programme and abstracts from the 5th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, 8-11 July 2003, Paris and are published in Antiviral Therapy Volume 8 issue 4.

  1. Carr A, Martin A, Ringland C et al – Long term changes in lipodystrophy after switching from thymidine nucleoside analogues to abacavir. Abstract 16.
  2. Raghavan S, Shlay JC et al – Rates of change in body composition among antiretroviral-naïve HIV-infected patients randomised to a didanosine/stavudine versus abacavir/lamivudine containing regimen in the Flexible Initial Retrovirus Suppressive Therapies (FIRST) study (CPCRA 058). Abstract 13.

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