Body fat changes and blood fat abnormalities in children taking antiretroviral therapy remain relatively stable over two years follow-up, according to a study presented earlier this month at the Thirteenth Conference on Retroviruses and Opportunistic Infections in Denver. In addition, the same group of doctors found that switching young patients from an HIV treatment combination containing d4T (stavudine, Zerit) led to an incomplete recovery of fat loss after almost two years.
Lipodystrophy, which involves changes in fat levels in the blood or changes in the distribution of body fat, is a common problem in patients taking certain types of antiretroviral therapy. While many studies have examined this group of side-effects in adult patients, few studies have examined them in children taking HIV treatment.
Stability of lipodystrophy
To assess whether lipodystrophy changed over time, investigators from Milan and London recruited 55 children and adolescents with lipodystrophy during 2003. The investigators examined the children again in late 2004, when they were aged between eight and 22 years, with a median age of 14. Fifty-four (98%) of the patients were taking anti-HIV treatment, with one patient having stopped HIV therapy at the age of 15.
Twelve (22%) of the patients had fat loss under the skin and eight (15%) had fat build-up around the internal organs. None of these patients showed any change in body fat composition over the follow-up period. Body fat changes were diagnosed visually.
A further 28 (51%) of the patients had both fat loss under the skin and fat gain around the organs. In 13 (46%) of these patients, body fat redistribution became worse, with three patients developing severe fat gain.
In contrast, seven patients’ body fat changes got better over the follow-up period. These included four patients with fat loss under the skin, one with fat gain around the organs and two with both conditions.
When they examined blood fat levels, the investigators found high cholesterol levels in 23 (42%) of the patients at the start of the study. This resolved in 14 patients, but five new cases developed over the follow-up period. High cholesterol was defined as a level over 200mg/dl
Similarly, triglyceride levels over 150mg/dl were seen in 15 (27%) of the patients at the start of the study. These resolved in eight patients, but twelve new cases arose.
Although ten of the patients received treatment with recombinant human growth hormone or fenofibrate (Lipantil / Supralip 160), only one of these patients showed an improvement in body fat composition.
“Lipodystrophy syndrome arising in childhood does not appear to resolve in the majority of cases,” conclude the investigators, “ although, once established, symptoms of fat redistribution seemed relatively stable.”
Effects of switching drugs
In a further study, the Milan team examined the effects of switching HIV drugs in a cohort of 24 HIV-positive patients aged between five and 20 years. All of the children and adolescents had been taking a protease inhibitor with d4T and 3TC (lamivudine, Epivir) for at least a year, and had signs of fat loss.
Adult studies have shown a modest improvement in limb fat levels after d4T is replaced with either abacavir (Ziagen) or tenofovir, but similar strategies have not been tested in younger patients.
The investigators replaced d4T with tenofovir and the protease inhibitor with efavirenz, measuring body fat composition using dual-energy X-ray absorptiometry (DEXA) scans before switching and again 96 weeks later.
Compared to a group of 24 healthy volunteers of similar age, the HIV-positive patients had significantly less fat on their arms and legs at the start of the study (p
Although the investigators did not include a comparison group that remained on the d4T-containing treatment regimen, these results suggest that replacement of d4T and a protease inhibitor results in normal development of fat under the skin in children and adolescents, at least for two years after the treatment switch. However, this strategy does not replace the fat which has already been lost as a side-effect of prolonged HIV treatment.
The treatment switch did not affect the patients’ HIV or CD4 T-cell levels. All of the patients maintained viral loads below 50 copies/ml, while CD4 cell counts and percentages were stable across the study.
Viganò A et al. Prospective follow-up of HIV-infected children and young people with lipodystrophy. Thirteenth Conference on Retroviruses and Opportunistic Infections, Denver, abstract 692, 2006a.
Viganò A et al. Improvement in lipoatrophy associated with highly active antiretroviral therapy in HIV-infected children and adolescents switched from stavudine to tenofovir. Thirteenth Conference on Retroviruses and Opportunistic Infections, Denver, abstract 693, 2006b.