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

Abstract

ObjectiveLongitudinal 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.MethodsWe 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.ResultsIn 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).ConclusionsOur 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.

Nutrition in HIV-Infected Infants and Children: Current Knowledge, Existing Challenges, and New Dietary Management Opportunities

“…Associations between abnormal body fat distribution and pediatric HIV disease have been established in various studies (60)(61)(62). HIV infection itself is a factor that causes lipodystrophy syndrome in children who are being treated with antiretroviral medications (63) and could refer to abnormal fat accumulation (lipohypertrophy) or localized loss of fatty tissue (lipoatrophy) (64).…”

Associations Between Central Obesity and Lifelong Antiviral Therapy in Adults Living With HIV Acquired From Early Childhood

“…The etiologies of these complications in PLWH are not entirely known but may be associated with a complex interaction between consequences of the virus itself, chronic use of ARVs, and underlying inflammatory processes. Previous studies have demonstrated a link between metabolic abnormalities, lipodystrophy, and most classes of ARVs, including nucleoside reverse transcriptase inhibitors (NRTIs), 4,5 non-NRTIs, 6 and protease inhibitors (PIs). 7,8 More recently, the advent of integrase strand transfer inhibitors, in particular dolutegravir, has also been associated with considerable weight gain and other related metabolic complications.…”

Switch to Efavirenz Attenuates Lipoatrophy in Girls With Perinatal HIV

“…Based upon data from UNAIDS-Joint United Nations Programme on HIV/AIDS there are approximately 5.2 million children, adolescents, and young adults living with HIV younger than 24 years globally. Prior descriptive studies have demonstrated that exposure to PIs (7)(8)(9), NRTIs (9)(10)(11)(12), and NNRTI (8) alone or in combination contribute to lipodystrophy. Lipodystrophy can be disfiguring and stigmatizing for CHIV.…”