Abstract
BackgroundDespite changes in WHO guidelines, stavudine is still used extensively for treatment of pediatric HIV in the developing world. Lipoatrophy in sub-Saharan African children can be stigmatizing and have far-reaching consequences. The severity and extent of lipoatrophy in pre-pubertal children living in sub-Saharan Africa is unknown.MethodsIn this cross-sectional study, children who were 3-12 years old, on antiretroviral therapy and pre-pubertal were recruited from a Family HIV Clinic in South Africa. Lipoatrophy was identified and graded by consensus between two HIV pediatricians using a standardized grading scale. A professional dietician performed formal dietary assessment and anthropometric measurements of trunk and limb fat. Previous antiretroviral exposures were recorded. In a Dual-Energy X-ray Absorbtiometry (DXA) substudy body composition was determined in 42 participants.ResultsAmong 100 recruits, the prevalence of visually obvious lipoatrophy was 36% (95% CI: 27%–45%). Anthropometry and DXA measurements corroborated the clinical diagnosis of lipoatrophy: Both confirmed significant, substantial extremity fat loss in children with visually obvious lipoatrophy, when adjusted for age and sex. Adjusted odds ratio for developing lipoatrophy was 1.9 (95% CI: 1.3 - 2.9) for each additional year of accumulated exposure to standard dose stavudine. Cumulative time on standard dose stavudine was significantly associated with reductions in biceps and triceps skin-fold thickness (p=0.008).ConclusionsThe prevalence of visually obvious lipoatrophy in pre-pubertal South African children on antiretroviral therapy is high. The amount of stavudine that children are exposed to needs review. Resources are needed to enable low-and-middle-income countries to provide suitable pediatric-formulated alternatives to stavudine-based pediatric regimens. The standard stavudine dose for children may need to be reduced. Diagnosis of lipoatrophy at an early stage is important to allow timeous antiretroviral switching to arrest progression and avoid stigmatization. Diagnosis using visual grading requires training and experience, and DXA and comprehensive anthropometry are not commonly available. A simple objective screening tool is needed to identify early lipoatrophy in resource-limited settings where specialized skills and equipment are not available.
Highlights
Despite changes in World Health Organization (WHO) guidelines, stavudine is still used extensively for treatment of pediatric HIV in the developing world
We explored the prevalence and risk factors for lipoatrophy in a group of pre-pubertal South African children on antiretroviral therapy (ART)
Lipoatrophy was identified and graded by consensus between two HIV pediatricians who were experienced in identifying lipoatrophy, using the following lipoatrophy grading scale defined by existing literature [9,10,11]: 0 – No fat changes; 1 – Possible minor changes, noticeable only on close inspection; 2 - Moderate changes, readily noticeable to an experienced clinician or a close relative who knows the child well; 3 – Major changes, readily noticeable to a casual observer
Summary
Despite changes in WHO guidelines, stavudine is still used extensively for treatment of pediatric HIV in the developing world. Lipoatrophy in sub-Saharan African children can be stigmatizing and have far-reaching consequences. The severity and extent of lipoatrophy in pre-pubertal children living in sub-Saharan Africa is unknown. In contrast to the developed world, stigmatization due to HIV in communal sub-Saharan African cultures may lead to loss of access to communally-held resources, loss of housing, denial of schooling, denial of healthcare, loss of employment or livelihood, secondary stigmatization of family members and physical violence [2,3]. ART-induced lipoatrophy may not be reversible, since lipoatrophy involves apoptosis of adipocytes [4], as opposed to nutritional wasting where adipocyte fat stores shrink but the cell survives. Fear of developing lipoatrophy may cause caregivers to become non-adherent with ART, leading to loss of CD4 cells, subsequent opportunistic infection and possibly death. In multivariate logistic regression modeling, fat distribution abnormalities due to ART were an independent risk factor for subsequent non-adherence in adults [5]
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