CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

and children exhibit impaired growth, mitochondrial toxicity, and immune dysregulation compared to their HIV-unexposed peers. However, the long-term sequelae of in utero HIV and ART exposure, particularly in resource-adequate settings, has not been well examined. We hypothesized that metabolic and immune abnormalities entrained by in utero HIV exposure may predispose to obesity and reactive airway disease (RAD) later in life. Methods: We leveraged the Partners HealthCare Research Patient Data Registry (RPDR, Boston) to compare long-term health outcomes among HEU adolescents and matched controls, and to determine maternal factors associated with adverse HEU outcomes. An RPDR search was performed to identify HEU individuals born since 1990 with medical records available at age ≥13 y. Over 200,000 controls also were retrieved from RPDR and matched up to 3:1 on birthdate (±5 y), age of last encounter (±2 y), sex, race, and zip code (SAS 9.4). Charts were manually reviewed to confirm HEU status and to extract medical information. BMI was standardized for age and sex using CDC growth charts. Obesity was defined as BMI ≥30kg/m^2 or ≥95 percentile. RAD was by clinical report. Results: 50 HEU young adults (18 [15,20] y, 54%male) and 141 matched controls (19 [16,21] y, 55%male) were compared. Mothers of HEU adolescents were aged 30±4 y with HIV for 4 [1,7] y. CD4 count was 405 [222,615]/mm^3 with 93% receiving prenatal ART. Obesity was seen in 42% of HEU adolescents compared to 25% of controls (P=0.04). BMI z-score was higher in HEU than controls (1.1±1.1 vs. 0.73±1.1, P=0.03). The prevalence of RAD also was higher in HEU than controls (40% vs. 24%, P=0.04). Within the HEU group, there was a strong inverse correlation between log-transformed maternal third-trimester CD4 and adolescent BMI z-score (r= -0.47, P=0.01). This relationship persisted upon adjustment for prenatal maternal factors including age, BMI, ART, and HIV duration (P<0.05). Prenatal maternal CD4 nadir, peak HIV viral load, HIV duration, and ART were not associated with adolescent BMI z-score. Unlike obesity, maternal factors did not relate to RAD among HEU. Conclusion: In utero HIV exposure and maternal immune dysregulation may predispose to obesity and RAD in adolescence. To our knowledge, this cohort represents the oldest group of HEU individuals to be compared to general population controls.

viral reservoirs in in utero infected infants including FL transcribed HIV DNA and PT compared to plasma HIV RNA Methods: As part of a trial of infant HIV prophylaxis to prevent IP MTCT a subset of non breast-fed HIV infants defined as IP(14) or IU( 13)by - HIV DNA /RNA or + at birth (resp).Infants with adequate samples birth,2,4-6,12, and 24 wks were chosen.Genomic DNA isolated with phenol/chloroform from PBMCs and HIV-1 DNA quantified by ddPCR.cp/million/PBMC Primer/probe pairs targeted full-length HIV reverse transcripts at the LTG-gag junction (SR1/M661/ZXF-FAM) and partials(SR1/AA55/ZXF-FAM) run in parallel with cellular beta-Globin (BGF1/ BGR1/BGX1-HEX). Unintegrated HIV cp/ per million were calculated by the difference of full length and partials. Results: We assessed PT and FL HIV DNA by ddPCR in 14 IP infected infants at birth,2,4-6,12 and 24 wks and found that 12/14 (85%) had P/FL or both prior to HIV RNA detection. 8 were detectable at birth and 5/6 who received 6 wks ZDV prophylaxis group A had detection at birth, the remainder became positive by 2 +wks. In IU (13) infected infants, we found both FL HIV DNA ( O-68,000 cp/ million ),Partials (142-154,000 cp/million)which include FL and early transcripts as cp/millionPBMC and the difference which is early transcripts(2-86,000)as seen in Figure . FL (includes integrated HIV DNA) ranged from 1% to 100% of detectable HIV DNA. HIV RNA ranged from (8,000-5million cp/ml). Surprisingly, there was no clear relationship between HIV DNA levels and HIV RNA at birth. Most infants already had detectable HIV reservoirs at birth although the percentage of FL and early transcripts varied. Conclusion: Early detection of HIV proviral DNA by ddPCR in IP infected infants at birth or weeks prior to viremia has important implications for pathogenesis especially with enhanced 2NVP/ZDV and 3(NFV,3TC ZDV) drug ARV prophylaxis which reduced postpartum transmission by 50% .Likewise the quantity / differentiation of full lengthHIV DNA (including integrated)vs early transcripts at birth is an important measure of HIV reservoirs for early treatment CURE / Remission protocols

Poster Abstracts

797 MATERNAL HIV RNA AFTER DELIVERY IS CORRELATED WITH INFANT PRETREATMENT HIV RNA Maureen Sakoi-Mosetlhi 1 , Gbolahan Ajibola 1 , Kara Bennett 2 , Sikhulile Moyo 1 , Kenneth Maswabi 1 , Oganne Batlang 1 , Joseph Makhema 1 , Kathleen M. Powis 3 , Shahin Lockman 4 , Daniel R. Kuritzkes 4 , Michael D. Hughes 5 , Roger L. Shapiro 1 , Mathias Lichterfeld 4 1 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 2 Bennett Statistical Consulting, Inc, New York, NY, USA, 3 Massachusetts General Hospital, Boston, MA, USA, 4 Brigham and Women’s Hospital, Boston, MA, USA, 5 Harvard University, Boston, MA, USA Background: Detectable maternal HIV RNA at delivery is a strong risk factor for in utero mother-to-child HIV transmission (MTCT), but the impact of maternal HIV RNA level near delivery (in the setting of effective maternal antiretroviral treatment [ART]) on the early viral burden of HIV+ infants is not well studied. Methods: We enrolled 40 HIV+mother-infant pairs in the Early Infant Treatment Study (EIT) in Botswana, at < 7 days from delivery. All infants had received prophylactic single-dose nevirapine and twice daily zidovudine per government protocol, up until HIV diagnosis by DNA PCR using the Roche TaqMan. HIV RNA was performed using Abbott HIV-1 m2000rt with a lower detectable limit of 40 copies/ml. Baseline HIV RNA for enrolled infants was compared with maternal HIV RNA values collected on the same day, as well as maternal ART regimen and duration of ART in pregnancy. Spearman’s correlation

796 DETECTION HIV DNA BY DDPCR BEFORE VIREMIA IN INTRAPARTUM & AT BIRTH IN IU INFANTS Yvonne Bryson 1 , Ruth Cortado 1 , Dimitrios Vatakis 2 , Irene J. Kim 1 , Jerome Zack 1 , Ting-Ting Wu 1 , Karin Nielsen-Saines 1 , Deborah Persaud 3 , for the HPTN/NICHD040 1 University of California Los Angeles, Los Angeles, CA, USA, 2 National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA, 3 Johns Hopkins University, Baltimore, MD, USA Background: HIV MTC Transmission occurs during gestation in utero (+ at birth),or intrapartum IP(HIV- at birth) and positive 4-6 wks of life or later if breast- fed. Using ddPCR as a sensitive method of quantitating proviral HIVDNA including full length(FL)/partial transcripts(PT), we assessed early events in IP infected infants prior to detectable viremia and HIV proviral DNA as a measure of

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