CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

802 OUTCOMES OF NEONATES WITH RAPID HIV TREATMENT IN US: TREATING INFANTS EARLY STUDY Theodore Ruel 1 , Rohan Hazra 2 , Patrick Jean-Philippe 3 , Delia Rivera- Hernández 4 , Andres Camacho-Gonzalez 5 , Ann Chahroudi 5 , Rana Chakraborty 5 , Estafania Guerreros 1 , Kristin Hoeft 1 1 University of California San Francisco, San Francisco, CA, USA, 2 National Institute of Child Health and Human Development, Bethesda, MD, USA, 3 National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA, 4 University of Miami, Miami, FL, USA, 5 Emory University, Atlanta, GA, USA Background: While several international trials are testing strategies of early antiretroviral therapy (ART) for infants with HIV, little is known about the outcomes of perinatally infected infants in clinical (non-research) settings, in which neonatal ART options are limited. The Treating Infants Early Study (TIES) is an observational cohort study that aims to describe the management, safety, efficacy of ART initiated at < 6 weeks of life in communities throughout the USA. Methods: Informed consent was obtained by phone or in person, with paper or electronic documentation. Eligibility criteria were HIV diagnosis, age < 2 years, and ART start at < 6 weeks of life. Maternal, birth and ART history, and clinical outcomes were abstracted frommedical records, collected periodically during follow up. Descriptive statistics were used for this analysis. Results: Among 38 infants screened from Dec. 2015 to Sept. 2018, 15 enrolled, providing median (range) follow-up of 19(1-32) months; one was excluded from analysis due to prior research participation. Infants were born at 37(28-40) weeks gestation weighing 2.7 (1.1-3.9) kg to mothers 24 (15-36) years old, 6(43%) of whomwere diagnosed with HIV in labor. Infants received zidovudine (ZDV)(n=2), ZDV + 3 doses nevirapine(NVP) with(n=7) or without(n=2) lamivudine (3TC), or ZDV/3TC+NVP twice daily at treatment doses(n=2) prior to HIV diagnosis. ART as treatment was initiated at 8.5 (0-36) days of life: ZDV/3TC + NVP(n=12) or lopinavir/ritonavir(n=2). First CD4 count was 2,390(231-4,190) cells/µl, CD4%was 46(10-66) and HIV RNA was 3.7(1.9-5.0) log10 copies/ ml. While 8(53%) and 5(33%) were diagnosed with anemia and neutropenia respectively, ART was never interrupted, and regimens were later changed for anticipated efficacy and tolerance, but not toxicity. With heterogeneity in baseline plasma HIV RNA level and initial response (figure), suppression (RNA 200 c/ml, at 295 days), but many had early and prolonged suppression (e.g. 66 through 958 days of life). Conclusion: Most infants with HIV in this cohort had initiated ART before 9 days old, underscoring the need for potent and safe ART options in the neonatal period. With rapid and durable virologic suppression, some perinatally infected infants treated in community settings are likely to have low reservoir levels and be good candidates for future studies of remission strategies

803 HIV PERSISTS IN DIFFERENTIATED MEMORY CD4 T CELLS IN ART- SUPPRESSED CHILDREN

Marta Massanella 1 , Jintanat Ananworanich 2 , Louise Leyre 1 , Thidarat Jupimai 3 , Julie Mitchell 4 , Panadda Sawangsinth 5 , Mark de Souza 5 , Piyarat Suntarattiwong 6 , Kulkanya Chokephaibulkit 7 , Lydie Trautmann 4 , Thanyawee Puthanakit 3 , Nicolas Chomont 1 , for the HIVNAT209 and HIVNAT194 study groups 1 Université de Montréal, Montreal, QC, Canada, 2 US Military HIV Research Program, Bethesda, MD, USA, 3 Chulalongkorn University, Bangkok, Thailand, 4 Henry M Jackson Foundation, Bethesda, MD, USA, 5 SEARCH, Bangkok, Thailand, 6 Queen Sirikit National Institute of Child Health, Bangkok, Thailand, 7 Mahidol University, Bangkok, Thailand Background: HIV primarily persists in memory CD4 T cells in adults on antiretroviral therapy (ART). However, less is known about the HIV distribution in the pediatric population. We sought to identify the main cellular reservoirs for HIV in ART-suppressed Thai children and assess the inducibility of these genomes by evaluating their ability to produce viral proteins upon stimulation. Methods: Enriched CD4 T cells from 5 vertically infected, early treated children (ART initiation within 3.5 months of life and median age of 2.5 years) were stimulated with PMA/ionomycin in the presence of brefeldin A to maintain the expression of cell surface markers. After 24h, naïve (CD45RA+CCR7+CD27+), central memory (CM, CD45RA-CCR7+CD27+), transitional memory (TM, CD45RA-CCR7-CD27+) and effector memory (EM, CD45RA-CCR7-CD27-) cells were sorted by flow cytometry. Integrated HIV DNA was quantified in the sorted subsets by real-time PCR. The frequency of cells producing the HIV protein Gag was measured by flow cytometry using a novel assay detecting p24 expression with high specificity. Results: We first measured the frequency of each subset within the CD4 compartment. As expected, naïve cells represented the vast majority of CD4 T cells (median frequency of 84%), whereas CM, TM and EM were underrepresented (10%, 2% and 1%, respectively, Table 1). In spite of their high frequencies, naïve cells were rarely infected (median 45 [0-103] HIV DNA copies/106 cells). Most proviruses were detected in memory subsets, particularly in the EM subset which included the highest levels of cells harboring integrated genomes (median 10,943 [3,398-162,594] copies/106 cells) followed by TM and CM subsets (median 1,253 [172-11,571] and 206 [132-9,806] copies/106 cells, respectively). Although EM cells represented a small fraction of all CD4 T cells, their contribution to the HIV reservoir was higher than CM and TM cells (median 54%, 30% and 4%, respectively). Despite these high levels of HIV DNA, p24-producing cells were not detected in any of the pediatric samples tested upon stimulation. In contrast, p24+ events were detected in CD4 T cells from suppressed adults with comparable HIV DNA levels. Conclusion: In vertically infected children on ART, the large naïve compartment minimally contributes to the HIV reservoir. Although high levels of HIV DNA are present in memory cells, these proviruses did not produce detectable levels of p24 protein, suggesting that the latent reservoir is poorly inducible in ART- suppressed children.

Poster Abstracts

CROI 2019 312