1343. Body fat and metabolic complications in youth with perinatally-acquired HIV
Authors: Dirajlal-Fargo Sahera , Jacobson Denise L , Yu Wendy , Mirza Ayesha , Geffner Mitchell E , McComsey Grace A , Jao Jennifer 
Published: December 2022

Abstract

Background
The role of obesity on long-term metabolic complications remains poorly understood in youth living with perinatally-acquired HIV (YPHIV).

Methods
The PHACS Adolescent Master Protocol (AMP) study enrolled YPHIV from 2007-2009 across 15 U.S. sites, including Puerto Rico. We included YPHIV aged 7-19 yr with body composition data assessed by whole-body dual energy x-ray absorptiometry (DXA) at baseline and 2 years later. Metabolic outcomes included homeostatic assessment of insulin resistance (HOMA-IR) and non-high-density lipoprotein cholesterol (non-HDL-C). We fit linear regression models using generalized estimating equations to assess the association of % change in body and trunk fat over 2 yr with metabolic outcomes at years 2 and 3, adjusted for potential confounders (age, race: Black vs. non-Black, Tanner stage, sex, family history, CD4, viral load, and ART).

Results
232 participants had a second DXA and either HOMA-IR or non-HDL-C measured at year 2. Participant characteristics at the first DXA were: median (Q1, Q3) age 12 yr (9, 14) 70% Black, CD4 count 714 cells/mm3; 70% with HIV RNA &lt; 400 copies/mL; 72% on protease inhibitor-, 25% on non-nucleoside reserve transcriptase inhibitor-, and 3% on integrase strand transfer inhibitor-based ART. The median % increase from baseline in total body and trunk fat percentage at 2 yr was 5.41% and 4.47%, respectively. The figure shows distributions of HOMA-IR and non-HDL-C. In both unadjusted and adjusted analyses (Table), for every 1% increase in total body fat percentage from baseline to 2 years, we observed a 0.002 (95%CI -0.0, 0.005) higher log10 HOMA-IR at year 3, which equals ∼ a 0.5% higher HOMA-IR. For every 1% increase in total body and trunk fat percentage over 2 years, non-HDL-C (mg/dL) was 0.19 (95%CI 0.03, 0.35) higher and 0.65 (95%CI 0.12, 1.19) higher, respectively, in unadjusted models. Results were similar but slightly attenuated when we additionally adjusted for confounders including ART. Figure:HOMA-IR and non-HDL cholesterol at baseline, year 2, and year 3Table:Unadjusted and adjusted models assessing the association of percent change in body fat and trunk fat percentage with metabolic outcomes
¹Adjusted for age (years), sex (male vs female), race (Black vs non-Black), Tanner stage (2, 3, 4-5 vs 1), family history of diabetes or cardiovascular disease (yes, not known vs no), CD4 (≤350 vs &gt;350 cells/mm³), and viral load (≥400 vs &lt;400 copies/mL).
²Adjusted for age (years), sex (male vs female), race (Black vs non-Black), Tanner stage (2, 3, 4-5 vs 1), family history of diabetes or cardiovascular disease (yes, not known vs no), CD4 (≤350 vs &gt;350 cells/mm³), viral load (≥400 vs &lt;400 copies/mL), and ARV exposure (PI without NNRTI, NNRTI without PI vs other).

Conclusion
Increases in adiposity over time may lead to downstream decreased insulin sensitivity and dyslipidemia in YPHIV. This is clinically significant, as even small increases in HOMA-IR have been associated with all-cause mortality in non-diabetic HIV-uninfected adults. Long-term follow-up is warranted.

Disclosures
Mitchell E. Geffner, MD, Adrenas: Advisor/Consultant|Adrenas: Honoraria|Ascendis: Advisor/Consultant|Ascendis: Honoraria|Aventria: Honoraria|Eton: Advisor/Consultant|Eton: Honoraria|ICON Clinical Research, LLC/Aeterna Zentaris: Advisor/Consultant|ICON Clinical Research, LLC/Aeterna Zentaris: Honoraria|McGraw-Hill: Royalties|Neurocrine Biosciences: Grant/Research Support|Novo Nordisk: Grant/Research Support|Nutritional Growth Solutions Ltd: Advisor/Consultant|Nutritional Growth Solutions Ltd: Honoraria|Pfizer, Inc.: Advisor/Consultant|Pfizer, Inc.: Honoraria|Spruce Biosciences: Grant/Research Support|UpToDate: Royalties Grace A. McComsey, MD, Gilead, Merck, ViiV, Janssen, Theratechnologies: Advisor/Consultant.