CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

Conclusion: Poorer virologic suppression in infants who initiated ART ≥ 2013 compared to earlier years is a major concern, especially as infants starting in recent years had higher CD4% and lower VL at ART initiation. Further research is needed to understand reasons for worse VL outcomes in recent years. Ongoing monitoring of these infants is crucial to determine the long-term impact of poorer early viral suppression.

mortality, but there is limited data in children. We investigated sCD163 levels in HIV+ children and their correlations with intestinal damage, immune activation and disease progression. Methods: In a Kenyan cohort aged 5-20 years of 77 perinatally-infected HIV+ children, with 44 ART-naive (ART-) and 33 virally suppressed on ART (ART+), and 45 HIV unexposed-uninfected (HIV-) controls, we measured sCD163 and intestinal fatty acid binding protein (I-FABP) plasma levels by ELISA (R&D Systems). T cell activation and proliferation cytokine IL-2 were analyzed by flow cytometry on PBMCs with markers CD4, CD8, CD45RO, CD38, HLA-DR, and IL-2. Statistical analysis was performed on GraphPad Prismwith Kruskall-Wallis, Spearman’s correlation, and Wilcoxon tests. Results: ART- children have high sCD163 levels compared to HIV- (p=0.004) and ART+ (p=0.01) children, that decrease after 12 months of ART (p=0.02) to levels similar to HIV- controls. ART+ and HIV- children have equivalent sCD163 levels. In HIV+ children, sCD163 levels correlate with HIV disease progression indicated by %CD4 T cells, (p=0.0002, r=-0.41), HIV viral load (p<.0001, r=0.65), and CD4:CD8 T cell ratios (p=0.001, r=-0.36). sCD163 also associates with I-FABP, a marker of gut mucosal disruption (p=0.005, r=0.32). sCD163 correlates with CD4 and CD8 T-cell activation measured by CD38 and HLA-DR coexpression (CD4: p<0.0001, r=0.50; CD8: p=0.001, r=0.36) in HIV+ but not in HIV- children. Finally, there is an indirect correlation between sCD163 and IL-2+ memory CD4 T cells (p=0.0003, r=-0.42). Conclusion: Untreated HIV+ children have elevated sCD163 levels that normalize with ART. Elevated sCD163 levels correlate with advancing HIV disease, marked by increasing viral load and decreasing %CD4 and CD4:CD8 ratios. Compromised gut barriers and microbial translocation may trigger sCD163 release, as sCD163 directly associates with I-FABP. In HIV+ children, sCD163 strongly correlates with T cell activation, linking inflammation in the innate and adaptive immune systems. Last, the inverse correlation between sCD163 and IL-2 suggests a potential inhibitory role for sCD163 on T cell proliferation. Overall, high sCD163 levels in HIV+ children reflect gut mucosal disruption, global inflammation and disease progression. 861 VIROLOGIC RESPONSE TO ANTIRETROVIRAL THERAPY STARTED AT <12 WEEKS OF AGE Victoria Iyun 1 , Karl Technau 2 , Brian Eley 1 , Helena Rabie 3 , Andrew Boulle 1 , Geoffrey Fatti 4 , Frank Tanser 5 , Robin Wood 6 , Lee Fairlie 7 , Mary-Ann Davies 1 1 University of Cape Town, Cape Town, South Africa, 2 University of the Witwatersrand, Johannesburg, South Africa, 3 Stellenbosch University, Stellenbosch, South Africa, 4 Kheth’Impilo, Cape Town, South Africa, 5 University of KwaZulu-Natal, Durban, South Africa, 6 Desmond Tutu HIV Foundation, Cape Town, South Africa, 7 Wits Reproductive Health and HIV Institute, Johannesburg, South Africa Background: With recent shifts towards widespread effective prevention of mother-to-child transmission (PMTCT) coverage, and HIV birth testing implementation in South Africa allowing for initiation of antiretroviral therapy (ART) in the first weeks of life, the virologic and immunologic response of infants started on ART at <3 months of age may be different to previous periods. Evidence from large cohorts of infants receiving early ART outside of clinical trial environments is limited. We described the changes in virologic and immunologic outcomes during the first 6 months on ART according to time period of ART initiation. Methods: We analysed data from a retrospective cohort of HIV-infected infants who started ART aged <12 weeks from 2006-2016 at 8 South African sites within IeDEA-SA, and had ≥1 viral load (VL) measurement between 4-9 months on ART. Descriptive statistical analysis and logistic regression were conducted to describe viral suppression at 6 months on ART and identify determinants. We defined viral suppression as VL <400 copies/ml (cpm) and compared VL outcomes of infants who initiated ART in 2006-2009, 2010-2012 and ≥ 2013. Results: Of 710 HIV-infected infants included, 56%were female, median age at ART initiation was 9 weeks (Interquartile range (IQR): 5-11), median log 10 VL and CD4%were 5.86 (IQR: 4.8-6.4) cpm and 26.4 (IQR 18.6-37) respectively. The proportion of infants that achieved viral suppression by 6 months on ART decreased from 66% in 2006-09 to 50% in 2013-16 (P<0.015) and from 78% in 2006-09 to 58% in 2013-16 among 410 infants with additional VL measured at 12 months on ART. Median CD4 count by 6 months on ART was increased slightly among infants starting ART in 2013-16 vs. in earlier years (2096 vs. 1588 cells/ mm 3 , p<0.001). VL >1 million cpm and ART initiation ≥2013 were associated with lower odds of viral suppression at 6 months on ART (adjusted Odds Ratio (aOR): 0.43; 95% CI: 0.24-0.75 and aOR: 0.33; 95% CI: 0.18-0.61, respectively).

862 MATERNAL ANTIRETROVIRAL THERAPY IN PREGNANCY AND NEONATE PRETREATMENT VIRAL LOAD Faeezah Patel 1 , Stephanie Shiau 2 , Renate Strehlau 1 , Megan Burke 1 , Maria Paximadis 3 , Sharon Shalekoff 3 , Diana Schramm 3 , Caroline Tiemessen 3 , Elaine J. Abrams 2 , Louise Kuhn 2 1 Empilweni Service and Research Unit, Johannesburg, South Africa, 2 Columbia University, New York, NY, USA, 3 National Institute for Communicable Diseases, Johannesburg, South Africa Background: With expansion of effective maternal antiretroviral therapy (ART), rates of new infant HIV infections are low but a large proportion of infected infants are exposed to antiretrovirals before birth. We investigated relationships between maternal ART in pregnancy and pre-treatment (PT) viral load (VL) profiles in intrauterine-infected neonates. Methods: Between June 2014-September 2017, 79 neonates with confirmed HIV-infection were identified through a birth testing program at Rahima Moosa Mother and Child Hospital in Johannesburg, South Africa, and had a PT VL available in the neonatal period (28 days of life). VL was measured using the COBAS AmpliPrep/COBAS TaqMan HIV-1 test, v2.0 (Roche). Maternal VLs were measured during late pregnancy, at delivery or soon thereafter using the same assay. Other clinical characteristics were obtained through examination and record review. Results: Of the 79 intrauterine-infected neonates, 51.9%were female, mean birthweight was 2,843±565 grams and 88.6%were ≥37 weeks of gestation. 13.9% of mothers first learned their HIV status during admission for this delivery, 57% during this pregnancy, and 29.1% prior to this pregnancy. 18% of mothers received no ART before delivery, 37.2%<12 wks and 28.2%>12 wks of ART. All infants were given NVP prophylaxis prior to diagnosis. Neonate PT VL was measured at a median of 1 day (IQR: 1-6) with a median of 28,405 copies/ml (cpm) (IQR: 2,020-224,515) and 20.3% had a VL<1,000 cpm. Neonate PT VL was correlated with maternal VL (r=0.53, p<0.01). Neonate PT VL was significantly (p<0.01) lower (median 1,172 cpm) among those whose mothers received ART and had a maternal VL<1,000 cpm than among those whose mothers reported receipt of ART but with VL>1,000 cpm (median 38,400 cpm) or among those whose mothers had received no ART (median 42,542 cpm). Among neonates with PT VL<1,000 cpm, 47% had mothers on ART with maternal VL<1,000 cpm compared to 15% among neonates with PT VL>1,000 cpm (p=0.04). Conclusion: PT VL in these intrauterine-infected neonates was lower than expected and correlated with maternal VL. Most (>80%) mothers received ART during pregnancy and for those whose adherence with and duration of ART led to VL<1,000 cpm, the lowest neonate PT VLs were observed. Maternal ART during pregnancy may begin treatment of intrauterine infection.

Poster Abstracts

CROI 2018 326