Approximately a third of patients starting antiretroviral treatment in Senegal developed moderate to severe lipodystrophy, with the use of d4T being the sole risk factor, investigators report in a study published in the online edition of the Journal of Acquired Immune Deficiency Syndromes.
Lipodystrophy, a disturbance in the way the body stores and processes fat, was first widely described as a potential side-effect of antiretroviral therapy in 1998. Its prevalence and possible causes have been well-described in industrialised countries, but there is little information about lipodystrophy in resource-limited settings.
Investigators from Senegal undertook a study to describe the prevalence and causes of body fat changes in people with HIV, and to assess the impact of HIV treatment on lipids. Their study was case controlled, with 189 patients treated with anti-HIV drugs for between four and nine years matched with an HIV-negative individual of the same age and sex.
Changes in subcutaneous fat were assessed by the patients’ physicians, and blood samples were taken to measure the levels of blood fats. Measurements of skin folds were also taken, as were waist circumferences and waist-to-hip ratio.
The patients had a mean age of 42 years and 60% were women. The mean duration of HIV treatment was approximately five and a half years.
Earlier research has shown that the drugs most associated with fat loss (lipoatrophy) are d4T (stavudine, Zerit) and AZT (zidovudine, Retrovir). The HIV treatment of 83 patients in the Senegalese study involved AZT, with 63 individuals taking therapy that included d4T.
Moderate-to-severe lipodystrophy was diagnosed in 31% of patients. This included 13% of patients who had fat loss, 15% with fat gain, and 3% with a combination of both. Women were more likely than men to experience body fat changes after starting HIV treatment (34% vs 26%), but the difference was not statistically significant.
However, when the investigators employed a broader definition of lipodystrophy, they found that almost two-thirds of patients (65%) had developed body fat changes to same extent, ranging from mild to severe. This included 18% with fat loss, 36% with fat gain, and 12% with both.
Lipodystrophy was also assessed using body measurements. Using this method, 50% of patients were found to have developed body fat changes after starting HIV treatment.
The investigators also found that HIV-positive patients weighed significantly less than the controls (mean 64kg vs 72kg, p 2 vs 25.7kg/m2, p
Unsurprisingly, metabolic abnormalities were more common amongst the HIV-positive patients than the controls. Levels of fasting glucose (mean 4.86 mmol/l vs 3.60 mmol/l, p
Next the investigators compared the metabolic profiles of the HIV-positive patients with and without body fat changes. This showed that patients with such changes had significantly higher triglycerides (p = 0.0005), total cholesterol (p = 0.007) and LDL-cholesterol (p = 0.04).
Finally, the investigators conducted analyses to identify possible risk factors for the development of lipodystrophy. The only significant risk factor revealed by these was treatment with d4T (p
After a year of d4T treatment, 22% of patients had developed body fat changes, increasing to 40% after three years and 50% after five years of treatment with the drug.
“Thirty-one percent of subjects had moderate-severe lipodystrophy, and the only independent significant risk factor was stavudine therapy”, comment the investigators.
Mercier S et al. Lipodystrophy and metabolic disorders in HIV-1-infected adults on 4-to 9-year antiretroviral therapy in Senegal: A case-control study. J. Acquir Immune Defic Syndr (online edition), 2009.