Lipoatrophy/lipohypertrophy outcomes after antiretroviral therapy switch in children in the UK/Ireland.

Steve Innes,Intira Jeannie Collins,Mark Fredric Cotton,Justin Harvey,Ali Judd

doi:10.1371/journal.pone.0194132

Steve Innes, Intira Jeannie Collins + Show 3 more

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https://doi.org/10.1371/journal.pone.0194132

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Abstract

BackgroundFollowing widespread use of stavudine, a thymidine analogue, in antiretroviral therapy (ART) over the past three decades, up to a third of children developed lipoatrophy (LA) and/or lipohypertrophy (LH). Following phasing-out of stavudine, incidence of newly-diagnosed LA and LH declined dramatically. However, the natural history of existing cases should be explored, particularly with prolonged protease inhibitor exposure.MethodsThe Collaborative HIV Paediatric Study (CHIPS) is a multicentre cohort study of most HIV-infected children in the United Kingdom and Ireland. Those on ART with a LA/LH assessment recorded in 2003–2011 were included. Assessments were completed annually by consultant physicians. Using the 0–3 grading system, LA or LH was defined as grade 2 or 3. Resolution was defined as return to grade 1 or 0 in all body regions.ResultsOf 1345 children followed for median (IQR) 5.5 (2.9, 8.2) years after ART initiation, 30 developed LA and 27 developed LH, all at least 2 years after ART initiation. Median age at LA diagnosis was 11 (10, 13) years and at LH diagnosis was 13 (11, 15) years. Children with LA were more likely white (p<0.0001); lower height-for-age z-score at ART initiation (p = 0.02); initiated ART earlier (p = 0.04), with longer ART exposure (p = 0.04). Children with LH were similar to those without. Analysis of individual drugs revealed that LA was associated with greater duration of exposure to stavudine and didanosine; while LH was associated with greater duration of exposure to stavudine and ritonavir (given alone or in combination with another protease inhibitor). Median time in follow-up following ART switch was 2.8 (1.9, 4.9) and 2.5 (1.6, 4.7) years respectively. Resolution occurred in 10 (30%) of LA cases (median time to resolution 2.3 [1.8, 3.6] years) and 3 (11%) of LH cases (median time to resolution 2.0 [1.7, 2.1] years).ConclusionsPrevalence of LA and LH were low, with some resolution noted, especially for LA. More long-term data are needed.

Highlights

Antiretroviral therapy (ART)-related lipoatrophy (LA) is a disfiguring loss of subcutaneous fat, in the face, limbs and buttocks [1]
Of 1345 children followed for median (IQR) 5.5 (2.9, 8.2) years after ART initiation, 30 developed LA and 27 developed LH, all at least 2 years after ART initiation
Analysis of individual drugs revealed that LA was associated with greater duration of exposure to stavudine and didanosine; while LH was associated with greater duration of exposure to stavudine and ritonavir

Summary

Introduction

Antiretroviral therapy (ART)-related lipoatrophy (LA) is a disfiguring loss of subcutaneous fat, in the face, limbs and buttocks [1]. In the early days of the ART era, LA occurred in up to one-third of children on thymidine analogue ART, mainly stavudine, while LH appears related to protease inhibitors (PI) and efavirenz [7,8,9]. While the incidence of newly-diagnosed LA has declined dramatically, the natural history of existing cases remains uncertain [11,12,13,14]; the effect of prolonged PI exposure on LH is uncertain. Following widespread use of stavudine, a thymidine analogue, in antiretroviral therapy (ART) over the past three decades, up to a third of children developed lipoatrophy (LA) and/ or lipohypertrophy (LH). Following phasing-out of stavudine, incidence of newly-diagnosed LA and LH declined dramatically. The natural history of existing cases should be explored, with prolonged protease inhibitor exposure

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