d4T & fat wasting - more evidence

Further evidence that people who receive long-term treatment with d4T are more likely to suffer fat wasting compared with people receiving AZT was presented this week at the Eighth Annual Retroviruses Conference in Chicago.

The French Novavir study was originally designed to look at the effects of switching to one of two nucleoside backbones - d4T/3TC or AZT/3TC - in people with prior exposure to AZT, ddI or ddC, but an analysis to investigate differences in body fat changes was conducted after patients had been on treatment for two and half years. All patients received indinavir in this study, and the average duration of prior nucleoside analogue treatment at the time of the switch was 21 months in the d4T recipients and 24 months in the AZT recipients. The study thus approximates closely to the real world situation of many people who started HAART after several years of dual NRTI therapy in the mid-1990s, and it is the first prospective analysis in which the duration of total NRTI exposure is similar between the two arms of the study.

The study originally recruited 170 patients; 110 were included in the body fat analysis (those who experienced virological rebound and who consequently switched therapy before month 30 were excluded from this analysis). No baseline data on fat wasting was available, so any prior contribution of AZT, ddI or ddC could not be analysed, and the analysis did not control for which NRTIs were used prior to randomisation in the Novavir study.

After 30 months follow-up, no difference in fat accumulation was noted between the two arms, and no significant difference in any skinfold measures except for the thigh region could be found. D4T recipients had significant lower skinfold fat measurements in this area.

However, clinical signs of lipoatrophy (fat wasting) were significantly more frequent in the d4T recipients. 44% of the d4T group had 2 or more signs of fat wasting, compared with 18% of the AZT group (p=0.003), and overall, 70% of d4T recipients had some evidence of fat loss, compared to 43% of the AZT group.

There was no difference in metabolic parameters such as insulin levels, triglycerides or cholesterol levels.

Questioning from the floor after the presentation revealed that the analysis of clinical signs of lipoatrophy was unblinded; in other words, clinicians knew which drugs patients were taking, and if they believed that d4T causes fat loss, they may have looked harder for signs in patients taking d4T. It is also noteworthy, suggested some critics of the study, that only one region was found to differ significantly when skinfold thickness measurements were carried out.