Some HIV-infected adults develop lipodystrophy that includes significant changes in body
shape, with fat losses in the face, arms and legs, and fat gain in the trunk. This
lipodystrophy is often accompanied by other disorders of metabolism, such as increased
levels of fat and insulin in the blood.
The majority of these cases have been seen when patients are taking medications called
protease inhibitors. These are anti-retroviral medications designed to treat patients with
HIV. It is unclear if lipodystrophy is a result of having HIV or the medication used to
treat HIV. It has been suggested, but not proven, that lipodystrophy is a direct side
effect of protease inhibitors. In addition, it is unknown if HIV-infected children develop
significant lipodystrophy after taking protease inhibitors.
This study will investigate the prevalence of metabolic disorders and changes in body fat
distribution in children taking protease inhibitor anti-retroviral medications. The results
will be compared to three other groups; (1) children suffering from other non-HIV chronic
infections, (2) HIV-infected children not taking protease inhibitors, and (3) healthy
The study will look at HIV-infected children who have already started taking protease
inhibitors. It will evaluate these children for disorders in metabolism as well as body fat
changes. In addition, the study will follow HIV-infected children who will begin taking
protease inhibitors. The study will follow these children for 18 months to detect the
development of disorders in metabolism and / or body fat changes.
Some HIV-infected adults develop a lipodystrophy that includes significant changes in body
shape, with fat loss in the face, arms and legs, and fat gain in the trunk. This
lipodystrophy is often accompanied by hypertriglyceridemia, hypercholesterolemia, and
hyperinsulinemia. So far, almost all cases of lipodystrophy have occurred in patients
treated with protease inhibitor-containing antiretroviral therapies. Whether this
lipodystrophy is a result of the use of protease inhibitors or other therapies employed for
HIV infection, or is one of the many manifestations of HIV infection, and is unmasked by the
longevity achieved by those treated with protease inhibitors remains uncertain. It has been
suggested, although not proven, that this condition may be an adverse effect of protease
inhibitor treatment. It is also unknown whether HIV-infected children develop significant
lipodystrophy when exposed to protease inhibitors. We propose to investigate whether
initiation of protease inhibitor-containing antiretroviral regimens in children with HIV
infection affects the prevalence of dyslipidemia, insulin resistance, and alterations of
body fat distribution, and to study the pathophysiology of these changes. The incidence of
such abnormalities will be compared to children with non-HIV-related chronic infections, to
HIV-infected children who are treated with protease inhibitor sparing regimen, and to
This study has both cross-sectional and longitudinal components. Children with HIV
infection, who are to begin taking protease inhibitors and who are already taking protease
inhibitors as part of their treatment for HIV infection, will be recruited for a single
cross-sectional evaluation that will include studies of lipid and glucose metabolism and
body composition. In the longitudinal component, those children with HIV infection, who
were studied before they began taking protease inhibitors, will be followed prospectively
for 18 months to delineate further the relationships between treatment and the development
of lipodystrophy and abnormalities in lipid and glucose metabolism. If the cross-sectional
study does not show that the prevalence of lipodystrophy and its associated metabolic
alterations increases as a function of exposure to protease inhibitors, we will terminate
the prospective study. Changes in triglyceride levels, insulin levels, and regional body
fat will be evaluated as primary outcome measures. As part of the evaluations performed
during the cross-sectional and longitudinal studies, we will investigate the pathophysiology
of dyslipidemia in HIV-infected children by assessing lipoproteins and their subclasses,
apolipoproteins, and both lipoprotein lipase levels and activity.
FOR PROTEASE INHIBITOR-NAIVE HIV-INFECTED CHILDREN AND HIV-INFECTED CHILDREN ON PROTEASE
INHIBITOR-CONTAINING ANTIRETROVIRAL REGIMENS:
Evidence of HIV infection based on Center for Disease Control and Prevention criteria.
Enrollment on protocol 98-C-0041 or other HIV treatment protocol for children.
No other chronic disease unrelated to infection that may cause changes in body composition
or in lipid or glucose homeostasis.
No previous use of a protease inhibitor-containing antiretroviral regimen (PROTEASE
INHIBITOR-NAIVE HIV-INFECTED CHILDREN ONLY).
Data available concerning the start date of protease inhibitor treatment (HIV-INFECTED
CHILDREN ON PROTEASE INHIBITOR-CONTAINING ANTIRETROVIRAL REGIMENS ONLY).
HEALTHY PEDIATRIC VOLUNTEERS:
Good general health. No significant hematologic, renal, hepatic, endocrinologic, or
No evidence of HIV infection by standard HIV antibody testing.
Body mass index for age below 85th percentile.
Not currently using prescription medications on a continuing basis; the use of
over-the-counter medications will be reviewed on a case-by-case basis.
Stable clinical condition during evaluation.
CHILDREN WITH CONDITIONS CAUSING CHRONIC INFECTIONS OTHER THAN HIV:
Evidence of chronic, non-HIV-related infection such as chronic granulomatous disease,
hyperimmunoglobin E syndrome, etc.
Evidence of non-growth hormone-deficient growth failure, defined as a 12-month height
velocity at or below the fifth percentile for age using standard reference norms and by
No evidence of HIV infection by standard HIV antibody testing.
No current (last 2 months) use of sex steroid supplementation.
Enrollment in an ongoing NIH protocol for treatment of their disorders.
Age between 4 and 18 years.
No other chronic disease unrelated to infection that may cause either changes in body
composition or lipid or glucose homeostasis such as Type I diabetes mellitus,
lipodystrophic diabetes, Cushing's syndrome etc.
No inability to undergo MRI because of metal objects within their bodies that are
contraindications for MRI. These include cardiac pacemakers, neural pacemakers,
aneurysmal clips, schrapnel, ocular foreign bodies, cochlear implants, non-detachable
electronic or electromechanical devices.
No allergic reaction to heparin.