Dual class effect on lipodystrophy?

A study by Cohen and colleagues showed that the risk of developing lipodystrophy is vastly increased when nucleoside analogues are combined with protease inhibitors. This was a long-term study of treatment with dual protease inhibitors only (saquinavir/ritonavir), with some patients intensifying their treatment with two nucleoside analogues after 48 weeks (or due to viral rebound). Body composition was examined after three and four years on treatment to see whether the patients who added nucleosides had higher rates of lipodystrophy.

Analysis showed that 23% of those who had intensified treatment had developed three or more body fat abnormalities, yet none of those who received treatment solely with protease inhibitors had developed severe lipodystrophy. Less severe lipodystrophy, classified as one change, was seen in 18% of the PI-only group, and 44% of the PI + NRTI group. Further analysis showed that patients who added an NRTI to the protease inhibitors were eight times more likely to experience facial fat loss and six times more likely to lose buttock fat. Intensification with NRTIs resulted in an 8.4-fold increase in the risk of body fat changes after adjusting for age, baseline CD4 cell count, duration of prior NRTI treatment, and baseline viral load. However, rates of metabolic abnormalities were similar in the two groups.¹

However, one large randomised study (ACTG 5142) in the US found that after 96 weeks of treatment, lipoatrophy was 2.7 times more likely in people taking efavirenz versus lopinavir/r (Kaletra), when paired with dual NRTIs.² Although the majority of people in this study were taking AZT or d4T, the nucleoside analogues particularly linked to lipoatrophy, analysis showed that even in people taking tenofovir, lipdystrophy was more frequent in those taking efavirenz than in those taking lopinavir/ritonavir.