CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

Background: Adolescents living with perinatally-acquired HIV experience puberty later than HIV-exposed uninfected young people. This study describes growth during adolescence including regional variations. Methods: The CIPHER Cohort Collaboration pooled observational data from 1994-2015 from 48 countries. Adolescents who initiated a combination ART regimen before age 10 years and had ≥4 height measurements aged ≥8 years (including ≥1 measurement aged≥12 years for females and ≥14 years for males based on expected age at peak height velocity) were included. We used SITAR (Super Imposition by Translation And Rotation) models to describe growth from age 8-19 years using 3 parameters; mean height, timing and intensity (i.e. shape of the growth velocity curve) of the growth spurt. We then used multivariable regression models to explore characteristics (region, year of birth, initial ART regimen, age, height-for-age z-score (HAZ), and BMI- for-age z-score (zBMI) at ART initiation (baseline)) associated with the growth parameters from SITAR models. Results: Of 9397 female and 9585 males on ART by age 10, 4535 and 2202, respectively, were included. 1125(17%) were from Botswana and South Africa, 3312(49%) Eastern and rest of Southern Africa, 442(7%) Western and Central Africa, 880(13%) Europe and North America, 649(10%) Asia, 329(5%) Latin America. Timing of the growth spurt varied by region and sex (Figure). In multivariable analyses the association between baseline HAZ and timing of growth spurt in females differed by region (p=0.017); a 1SD decrease in HAZ was associated with a 0.30(95%CI 0.21,0.39) year delay in Asia and 0.11(0.07,0.14) year delay elsewhere. In males, there was an interaction between baseline age and HAZ (p=0.009); for males starting ART age <4 years, baseline HAZ was not associated with timing but for those initiating ART at older ages, lower baseline HAZ was associated with later growth spurts. Later calendar year of birth was associated with earlier growth spurt in females (-0.04(-0.07,-0.02)) but not in males. A 1SD decrease in zBMI was associated with a delay of 0.04(0.01,0.07) years in females and 0.07 (0.02,0.12) years in males. Differences in intensity of the growth spurt were observed across regions, age and HAZ at ART initiation. Conclusion: Starting ART when stunted is associated with delayed pubertal growth spurt globally. Longer term follow-up is important to understand the impact of these delays on outcomes later in life.

decrease in LS Z-score from> -2 to < -2, but 1 ALWH had this outcome in TB Z-score. Among participants with 24 week DXA results, 15/47 (32%) had either no change or decreased LS BMD after switch, with a mean change of -1.6%; 14/15 (93%) of this group were female. Overall, a greater proportion of females than males had either no change or decreased LS BMD (58% vs 4%, p<0.0001; Fisher Exact). Overall, statistically significant increases in serum creatinine and decreases in eGFR were observed (p<0.0001 and 0.0003, respectively); however, final levels remained within clinically acceptable limits. Conclusion: South African ALWH switching from ABC to TDF experienced statistically significant decreases in eGFR but not in LS and TB BMD overall. However, female ALWH experienced greater decreases in LS BMD and may require closer monitoring. 823 EPIGENETIC AGE IN YOUNG AFRICAN AMERICAN ADULTS WITH PERINATALLY ACQUIRED HIV Stephanie Shiau 1 , Michael T.Yin 2 , Christian Vivar Ramon 2 , Grace Jang 2 , Anyelina Cantos 2 , Jayesh Shah 2 , Stephen M. Arpadi 2 1 Rutgers University, Piscataway, NJ, USA, 2 Columbia University Medical Center, New York, NY, USA Background: Prior studies have measured accelerated aging in people living with HIV (PLWH) using a DNA methylation (DNAm)-based biomarker of aging, “epigenetic age”, but data are limited in African Americans (AA). We assessed if perinatally-acquired HIV infection (PHIV) is associated with accelerated epigenetic age in AA young adults (20-35 years of age). Methods: We enrolled 61 AA young adults living in NYC, including 31 youth living with PHIV and 30 youth confirmed to be HIV seronegative (Controls) and measured DNAm fromwhole blood samples using the Illumina EPIC Array. DNAm age (years) was estimated by the Horvath method. We estimated four age acceleration measures, where positive values indicate that the blood sample is older than expected based on chronological age: 1) age acceleration residual (AAR), considered to be robust with respect to cell composition changes; 2) extrinsic epigenetic age acceleration (EEAA), up-weights the contributions of age-related blood cell counts; 3) intrinsic epigenetic age acceleration (IEAA), adjusts for cell type counts; 4) Houseman-adjusted age acceleration residual (HAAAR), adjusts for cell type proportions estimated by the Houseman method. Results: PHIV and Controls did not differ by sex (45 vs. 40%male), chronological age (26.2 vs. 28.0 years), or ethnicity (90% not Hispanic or Latino in both groups). Among PHIV, 63.0% had a viral load (VL) <50 copies/mL (cpm) and 37%>50 cpm. Blood cell composition differed between PHIV and Controls, largely driven by differential proportions of CD8 (0.36 vs. 0.25, p<0.01) and CD4 T-Cells (0.18 vs. 0.36, p<0.01). Chronological age and DNAm age were positively correlated (r=0.56, p<0.01). PHIV had a higher mean AAR (2.86±6.5 vs. -2.96±3.9, p<0.01) and EEAA (4.57±13.0 vs. -4.72±6.0, p<0.01) compared to controls. Among PHIV, AAR was higher in those with VL >50 cpm than those with VL <50 cpm (8.52±5.3 vs. 0.66±5.1, p<0.01). However, IEAA and HAAAR, the two age acceleration measures that adjust for blood cell composition did not differ between PHIV and Controls. Conclusion: Epigenetic age acceleration in blood was observed in AA young adults with PHIV using measures unadjusted for blood cell composition. However, after accounting for blood cell composition, there was no longer evidence of age acceleration associated with HIV. Future studies of accelerated aging in PLWH should consider the relationships between CD8 and CD4 T-cells and epigenetic age. 824 GLOBAL VARIATIONS IN PUBERTAL GROWTH IN ADOLESCENTS LIVING WITH PERINATAL HIV Siobhan Crichton 1 , Julie Jesson 2 , Marie-Hélène Aké-Assi 3 , Erik Belfrage 4 , Mary-Ann Davies 5 , Jorge Pinto 6 , Chloe A.Teasdale 7 , Nguyen Van Lam 8 , Rachel Vreeman 9 , Sebastian Wanless 10 , Paige L. Williams 11 , Marcel Yotebieng 12 , Valériane Leroy 2 , Ruth Goodall 1 , for the CIPHER Global Cohort Collaboration 1 MRC Clinical Trials Unit at UCL, London, UK, 2 INSERM, Toulouse, France, 3 University Hospital Yopougon, Abidjan, Cote d’Ivoire, 4 Karolinska University Hospital, Stockholm, Sweden, 5 University of Cape Town, Cape Town, South Africa, 6 Universidade Federal de Minas Gerais, Belo Horizonte, Brazil, 7 Columbia University, New York, NY, USA, 8 National Hospital of Pediatrics, Hanoi, Vietnam, 9 Indiana University, Indianapolis, IN, USA, 10 Texas Children’s Hospital, Houston, TX, USA, 11 Harvard T.H. Chan School of Public Health, Boston, MA, USA, 12 The Ohio State University, Columbus, OH, USA

Poster Abstracts

825 LONG-TERM NONPROGRESSION IN CHILDREN WITH PERINATALLY ACQUIRED HIV

Charlotte Jackson 1 , Alasdair Bamford 2 , Siobhan Crichton 1 , Ruth Goodall 1 , Philip J. Goulder 3 , Nigel Klein 4 , Laura Marques 5 , Paolo Paioni 6 , Andrew Riordan 7 , Vana Spoulou 8 , Vinicius A.Vieira 3 , Intira J. Collins 1 , for the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study group 1 MRC Clinical Trials Unit at UCL, London, UK, 2 Great Ormond Street NHS Foundation Trust, London, UK, 3 University of Oxford, Oxford, UK, 4 UCL Great Ormond Street Institute of Child Health, London, UK, 5 Centro Hospitalar do Porto, Porto, Portugal, 6 University Children's Hospital Zurich, Zurich, Switzerland, 7 Alder Hey Children’s NHS Foundation Trust, Liverpool, United Kingdom, 8 University of Athens, Athens, Greece Background: Long-term non-progression (LTNP) refers to long-term survival with HIV without disease progression or antiretroviral treatment (ART). LTNP prevalence estimates in children range from 2-42% using varied definitions, often in small samples. Understanding LTNP in children can potentially inform

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