Lipodystrophy on first-line ARV regimens common in Indian patients

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Lipodystrophy appears to be just as common in Indian patients receiving antiretroviral treatment as it is in the United States and Europe, according to a report from an HIV clinic in Pune, Western India, published in the June 1st edition of the Journal of Acquired Immune Deficiency Syndromes.

The study, which looked at a cross-section of patients who are paying for antiretroviral therapy at a large HIV outpatient clinic, is the first comprehensive study of lipodystrophy and lipid elevations in a setting where patients are receiving the recommended World Health Organization first line regimens of d4T/3TC/nevirapine or AZT/3TC/nevirapine.

Antiretroviral treatment has been associated with the development of fat loss or a mixed syndrome of fat loss and fat gain in different parts of the body (lipodystrophy), and the nucleoside analogues AZT and d4T have been particularly linked to fat loss. However, the incidence of lipodystrophy in populations in resource-limited settings is unknown.

Glossary

lipodystrophy

A disruption to the way the body produces, uses and distributes fat. Different forms of lipodystrophy include lipoatrophy (loss of subcutaneous fat from an area) and lipohypertrophy (accumulation of fat in an area), which may occur in the same person.

lipid

Fat or fat-like substances found in the blood and body tissues. Lipids serve as building blocks for cells and as a source of energy for the body. Cholesterol and triglycerides are types of lipids.

exclusion criteria

Defines who cannot take part in a research study. Eligibility criteria may include disease type and stage, other medical conditions, previous treatment history, age, and gender. For example, many trials exclude women who are pregnant, to avoid any possible danger to a baby, or people who are taking a drug that might interact with the treatment being studied.

lipoatrophy

Loss of body fat from specific areas of the body, especially from the face, arms, legs, and buttocks.

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

The Indian study excluded any patient who had been on treatment for less than one year or who had adherence of less than 95%. Patients who had switched from one nucleoside analogue backbone to another due to intolerance were also excluded. The study recruited 150 patients taking d4T/3TC/nevirapine and 30 patients taking AZT/3TC/nevirapine. A control group of symptom-free, HIV-positive patients (n=126) was also recruited.

Lipodystrophy was assessed by clinical examination and lipid levels were assessed by measurement after overnight fast, since this is known to provide a more accurate measure of lipids and glucose levels.

Patients had begun HIV treatment at a relatively advanced stage of HIV disease: just over one-third in each treatment group already had an AIDS-defining illness and the median CD4 cell count was 116 cells/mm3 in the d4T group and 134 cells/mm3 in the AZT group at baseline. By the time of assessment, patients had received a median of 18 months of treatment.

Lipoatrophy (fat loss) was detected in 26% of patients receiving d4T/3TC/nevirapine and 10% of those receiving AZT/3TC (p=0.08). Although this difference was non-significant, multivariate regression analysis showed that d4T treatment was the only factor associated with the development of lipoatrophy, with d4T-treated patients more than three times more likely to develop fat loss compared to controls (OR 3.3, p=0.04). Lipohypertrophy (fat accumulation) was detected in 23% and 16.7% respectively, and a mixed pattern of both fat loss from the limbs and face together with abdominal fat accumulation was found in 10% of the d4T-treated patients and 6% of the AZT-treated patients.

Treated patients had significantly higher triglyceride, total cholesterol and LDL cholesterol levels, suggesting an increased long-term risk of cardiovascular disease, with the highest triglyceride levels seen among d4T-treated patients.

Fasting hyperglycemia was significantly more common in treated patients, despite the fact that none of the patients was receiving a protease inhibitor, the antiretroviral drug class usually associated with this metabolicn abnormality in HIV-positive people.

“The psychologic and social consequences of lipodystrophy syndrome in the developing world, and their impact on the acceptance of antiretroviral therapy, need to be studied in detail,” note the authors.

References

Pujari SN et al. Lipodystrophy and dyslipidemia among patients taking first-line, World Health Organization-recommended highly active antiretroviral therapy regimens in western India. J Acquir Immune Defic Syndr 39: 199-202, 2005.