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Long-Term Changes of Subcutaneous Fat Mass in HIV-Infected Children on Antiretroviral Therapy: A Retrospective Analysis of Longitudinal Data from Two Pediatric HIV-Cohorts.

Cohen S, Innes S, Geelen SP, Wells JC, Smit C, Wolfs TF, van Eck-Smit BL, Kuijpers TW, Reiss P, Scherpbier HJ, Pajkrt D, Bunders MJ - PLoS ONE (2015)

Bottom Line: Fat mass in all limbs was decreased in HIV-infected children compared to controls (arm fat Z-score: coefficient -0.4813; P = 0.006, leg fat Z-score: coefficient -0.4345; P = 0.013).In the HIV-infected group, stavudine treatment was associated with lower subcutaneous fat mass (arm fat Z-score: coefficient -0.5838; P = 0.001), with an additional cumulative exposure effect (arm fat Z-score: coefficient -0.0867; P = 0.003).These results underline the need for early detection of subcutaneous fat loss and alternative treatment options for HIV-infected children globally.

View Article: PubMed Central - PubMed

Affiliation: Department of Paediatric Haematology, Immunology, and Infectious Diseases, Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.

ABSTRACT

Objective: Longitudinal studies objectively evaluating changes in regional fat distribution of HIV-infected children assessed by whole body dual energy X-ray absorptiometry (DEXA) are scarce, whilst this long-term effect of HIV and antiretroviral therapy (cART) is an important issue in infected children in need for lifelong treatment.

Methods: We assessed regional fat distribution over time, measured with sequential DEXA-scans in HIV-infected children on cART in cohorts from South Africa (SA) and the Netherlands (NL), and in healthy controls (SA). Limb and trunk fat Z-scores were calculated with the lambda-mu-sigma (LMS) method. Multivariable linear regression models with mixed effects were used to investigate the effect of cART compounds on body fat distribution over time.

Results: In total, 218 children underwent 445 DEXA assessments with a median follow-up of 3.5 years. Fat mass in all limbs was decreased in HIV-infected children compared to controls (arm fat Z-score: coefficient -0.4813; P = 0.006, leg fat Z-score: coefficient -0.4345; P = 0.013). In the HIV-infected group, stavudine treatment was associated with lower subcutaneous fat mass (arm fat Z-score: coefficient -0.5838; P = 0.001), with an additional cumulative exposure effect (arm fat Z-score: coefficient -0.0867; P = 0.003).

Conclusions: Our study shows that subcutaneous fat loss is still prevalent in HIV-infected children on cART, and is strongly associated with cumulative stavudine exposure. These results underline the need for early detection of subcutaneous fat loss and alternative treatment options for HIV-infected children globally.

No MeSH data available.


Related in: MedlinePlus

a. Left arm fat Z-scores of HIV-infected children over age.Black circles: scatterplot and locally weighted scatterplot smoothing line (LOWESS) of children exposed to stavudine; Grey triangles: scatterplot and LOWESS of children not exposed to stavudine. b. Left arm fat Z-scores of HIV-infected children over years of stavudine exposure. Black circles: scatterplot and locally weighted scatterplot smoothing line (LOWESS) of children exposed to stavudine.
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pone.0120927.g001: a. Left arm fat Z-scores of HIV-infected children over age.Black circles: scatterplot and locally weighted scatterplot smoothing line (LOWESS) of children exposed to stavudine; Grey triangles: scatterplot and LOWESS of children not exposed to stavudine. b. Left arm fat Z-scores of HIV-infected children over years of stavudine exposure. Black circles: scatterplot and locally weighted scatterplot smoothing line (LOWESS) of children exposed to stavudine.

Mentions: To evaluate the underlying factors explaining the loss of subcutaneous fat in HIV-infected children in these cohorts, we assessed associations between HIV-related parameters and specific antiretroviral compounds with regional fat mass over time. Univariable regression analyses of the left arm fat Z-score showed P-values <0.2 for gender, ethnicity, region of origin, CD4+ T-cell count, maximum WHO clinical stage, stavudine and lopinavir/r treatment. These variables were included in the multivariable model (Table 2). In the multivariable model, treatment with stavudine remained significantly associated with a lower left arm fat Z-score over time (coefficient -0.5838, P = 0.001) (Fig 1A) and there was a trend towards lower left arm Z-score over time in children treated with lopinavir/r (coefficient -0.2177, P = 0.099) (Table 2). Treatment with stavudine was also negatively associated with the arm fat versus lean ratio (coefficient -0.1670, P = 0.001). Lopinavir/r showed no association with this ratio (coefficient 0.0087, P = 0.778) (S1 Table). We further assessed whether a time-dependent effect of stavudine and lopinavir/r was present, by repeating the uni- and multivariable analyses and substituting the cART-exposure with the cumulative treatment duration of these antiretroviral compounds. Duration of treatment with stavudine was associated with a lower left arm fat Z-score over time (coefficient -0.0867, P = 0.003) as well as with the arm fat to lean ratio (coefficient -0·0294, P<0·001) (Table 2 and S1 Table). The left arm fat Z-score of the stavudine-treated HIV-infected children most markedly decreased in the first 2 years of exposure and then stabilized (Fig 1B). Longer duration of treatment with stavudine was borderline significantly associated with a decreasing leg fat Z-score (coefficient -0.0502, P = 0.051) (Table 3). In univariable analysis, a longer duration of treatment with lopinavir/r was associated with a lower left arm fat Z-score over time (coefficient -0.0781, P = 0.001), however when assessed in multivariable analysis the coefficient was -0.0403 with a P-value of 0.127 (Table 2).


Long-Term Changes of Subcutaneous Fat Mass in HIV-Infected Children on Antiretroviral Therapy: A Retrospective Analysis of Longitudinal Data from Two Pediatric HIV-Cohorts.

Cohen S, Innes S, Geelen SP, Wells JC, Smit C, Wolfs TF, van Eck-Smit BL, Kuijpers TW, Reiss P, Scherpbier HJ, Pajkrt D, Bunders MJ - PLoS ONE (2015)

a. Left arm fat Z-scores of HIV-infected children over age.Black circles: scatterplot and locally weighted scatterplot smoothing line (LOWESS) of children exposed to stavudine; Grey triangles: scatterplot and LOWESS of children not exposed to stavudine. b. Left arm fat Z-scores of HIV-infected children over years of stavudine exposure. Black circles: scatterplot and locally weighted scatterplot smoothing line (LOWESS) of children exposed to stavudine.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4493065&req=5

pone.0120927.g001: a. Left arm fat Z-scores of HIV-infected children over age.Black circles: scatterplot and locally weighted scatterplot smoothing line (LOWESS) of children exposed to stavudine; Grey triangles: scatterplot and LOWESS of children not exposed to stavudine. b. Left arm fat Z-scores of HIV-infected children over years of stavudine exposure. Black circles: scatterplot and locally weighted scatterplot smoothing line (LOWESS) of children exposed to stavudine.
Mentions: To evaluate the underlying factors explaining the loss of subcutaneous fat in HIV-infected children in these cohorts, we assessed associations between HIV-related parameters and specific antiretroviral compounds with regional fat mass over time. Univariable regression analyses of the left arm fat Z-score showed P-values <0.2 for gender, ethnicity, region of origin, CD4+ T-cell count, maximum WHO clinical stage, stavudine and lopinavir/r treatment. These variables were included in the multivariable model (Table 2). In the multivariable model, treatment with stavudine remained significantly associated with a lower left arm fat Z-score over time (coefficient -0.5838, P = 0.001) (Fig 1A) and there was a trend towards lower left arm Z-score over time in children treated with lopinavir/r (coefficient -0.2177, P = 0.099) (Table 2). Treatment with stavudine was also negatively associated with the arm fat versus lean ratio (coefficient -0.1670, P = 0.001). Lopinavir/r showed no association with this ratio (coefficient 0.0087, P = 0.778) (S1 Table). We further assessed whether a time-dependent effect of stavudine and lopinavir/r was present, by repeating the uni- and multivariable analyses and substituting the cART-exposure with the cumulative treatment duration of these antiretroviral compounds. Duration of treatment with stavudine was associated with a lower left arm fat Z-score over time (coefficient -0.0867, P = 0.003) as well as with the arm fat to lean ratio (coefficient -0·0294, P<0·001) (Table 2 and S1 Table). The left arm fat Z-score of the stavudine-treated HIV-infected children most markedly decreased in the first 2 years of exposure and then stabilized (Fig 1B). Longer duration of treatment with stavudine was borderline significantly associated with a decreasing leg fat Z-score (coefficient -0.0502, P = 0.051) (Table 3). In univariable analysis, a longer duration of treatment with lopinavir/r was associated with a lower left arm fat Z-score over time (coefficient -0.0781, P = 0.001), however when assessed in multivariable analysis the coefficient was -0.0403 with a P-value of 0.127 (Table 2).

Bottom Line: Fat mass in all limbs was decreased in HIV-infected children compared to controls (arm fat Z-score: coefficient -0.4813; P = 0.006, leg fat Z-score: coefficient -0.4345; P = 0.013).In the HIV-infected group, stavudine treatment was associated with lower subcutaneous fat mass (arm fat Z-score: coefficient -0.5838; P = 0.001), with an additional cumulative exposure effect (arm fat Z-score: coefficient -0.0867; P = 0.003).These results underline the need for early detection of subcutaneous fat loss and alternative treatment options for HIV-infected children globally.

View Article: PubMed Central - PubMed

Affiliation: Department of Paediatric Haematology, Immunology, and Infectious Diseases, Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.

ABSTRACT

Objective: Longitudinal studies objectively evaluating changes in regional fat distribution of HIV-infected children assessed by whole body dual energy X-ray absorptiometry (DEXA) are scarce, whilst this long-term effect of HIV and antiretroviral therapy (cART) is an important issue in infected children in need for lifelong treatment.

Methods: We assessed regional fat distribution over time, measured with sequential DEXA-scans in HIV-infected children on cART in cohorts from South Africa (SA) and the Netherlands (NL), and in healthy controls (SA). Limb and trunk fat Z-scores were calculated with the lambda-mu-sigma (LMS) method. Multivariable linear regression models with mixed effects were used to investigate the effect of cART compounds on body fat distribution over time.

Results: In total, 218 children underwent 445 DEXA assessments with a median follow-up of 3.5 years. Fat mass in all limbs was decreased in HIV-infected children compared to controls (arm fat Z-score: coefficient -0.4813; P = 0.006, leg fat Z-score: coefficient -0.4345; P = 0.013). In the HIV-infected group, stavudine treatment was associated with lower subcutaneous fat mass (arm fat Z-score: coefficient -0.5838; P = 0.001), with an additional cumulative exposure effect (arm fat Z-score: coefficient -0.0867; P = 0.003).

Conclusions: Our study shows that subcutaneous fat loss is still prevalent in HIV-infected children on cART, and is strongly associated with cumulative stavudine exposure. These results underline the need for early detection of subcutaneous fat loss and alternative treatment options for HIV-infected children globally.

No MeSH data available.


Related in: MedlinePlus