Switch from d4T improves body fat: 48 week results

Keith Alcorn
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This article is more than 22 years old.

TARHEEL is a 48-week, open-label switch study designed to assess whether lipoatrophy and hyperlactatemia improve when d4T is replaced with abacavir or AZT. Findings were first reported at the Ninth Conference on Retroviruses and Opportunistic Infections earlier this year.

This study has enrolled 118 individuals; 86 replaced d4T with abacavir (AZT-experienced individuals), and 32 with AZT. All participants had viral load below 400 copies/ml at the time of the switch, and at least six months of d4T experience. 95% maintained viral load below 400 copies at week 48.

This presentation provided evidence from DEXA scans taken 48 weeks after the treatment switch, and showed significant improvement in both groups. Fat levels in the arms had increased by 35.3% from baseline, whilst trunk fat and leg fat had increased by 16.4% and 12% respectively. CT scans indicated that the total increase in subcutaneous fat was 4%, whilst visceral fat declined by 2%. Seventy nine per cent of participants experienced an increase in subcutaneous fat, and 54% experienced a decrease in visceral fat.

Glossary

deoxyribonucleic acid (DNA)

The material in the nucleus of a cell where genetic information is stored.

subcutaneous

Beneath or introduced beneath the skin, e.g. a subcutaneous injection is an injection beneath the skin.

 

visceral

Pertaining to the internal organs. Visceral fat is fat tissue that is located deep in the abdomen and around internal organs.

 

p-value

The result of a statistical test which tells us whether the results of a study are likely to be due to chance and would not be confirmed if the study was repeated. All p-values are between 0 and 1; the most reliable studies have p-values very close to 0. A p-value of 0.001 means that there is a 1 in 1000 probability that the results are due to chance and do not reflect a real difference. A p-value of 0.05 means there is a 1 in 20 probability that the results are due to chance. When a p-value is 0.05 or below, the result is considered to be ‘statistically significant’. Confidence intervals give similar information to p-values but are easier to interpret. 

lipoatrophy

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

The same research group also reported the effect on mitochondrial DNA levels of a switch from d4T to abacavir or AZT. Several research groups have found that mitochondrial DNA levels are lower in the subcutaneous adipose tissue (fat) of people with lipoatrophy, and have argued that this is an effect of treatment with d4T, and the cause of fat wasting. However, not all researchers agree with these conclusions.

This study enrolled 16 individuals who had taken d4T for at least two years, and monitored changes in mt DNA over 48 weeks after these patients switched to abacavir (14) or AZT (2). DEXA results were reported for 12 patients, and indicated increases in arm, leg and trunk fat of 23%, 12% and 18%, respectively. At baseline seven of 16 had evidence of mitochondrial dysfunction, and median mitochondrial DNA levels were 174 per fat cell, compared to 863 per fat cell for 22 controls. Mitochondrial DNA levels in PBMCs and muscle tissue did not differ between the switch group and control group at baseline.

After 48 weeks mtDNA levels had risen to 453 per cell (n=11, p=0.01 as compared to Wk 0). Median muscle mt DNA was 1718 at Wk 0 (n=16), control 1427 (n=5), and 3538 at Wk 48 (n=12, p=0.11 as compared to Wk 0).

A weakness of this study is that it did not report mitochondrial DNA levels in subcutaneous adipose tissue, and did not include a control group of patients who continued to be treated with d4T. It is thus unclear whether drug effects on mitochondrial DNA are responsible for fat loss or fat restoration.

References

Flint O et al. NRTI effects on mitochondrial function are relevant to neuropathy but not to lipoatrophy. 42nd ICAAC, San Diego, abstract H-1925, 2002.

McComsey G et al. Improvements in mitochondrial (mt) DNA levels after substituting ABC or ZDV for d4T in HIV-infected patients with lipoatrophy (LA). 42nd ICAAC, San Diego, abstract H-1930, 2002.

Mccomsey G etal. CT scan findings at 48-wks confirm further regression of lipoatrophy (LA) following the substitution of stavudine (d4T) with either abacavir (ABC) or zidovudine (ZDV). 42nd ICAAC, San Diego, abstract H-1929, 2002.

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