CROI 2019 Abstract eBook

Abstract eBook

Oral Abstracts

HBV coinfection and its impact on HIV transmission and infant and maternal outcomes in HPTN 046, a HIV mother-to-child (MTCT) transmission study. Methods: HPTN 046 was a randomized controlled clinical trial of HIV MTCT which evaluated 6 months of infant nevirapine vs placebo for HIV prevention. Mother-infant pairs were enrolled in sub-Saharan Africa from 2007-2010; 1579 women (78%) also received ART. Maternal samples were retrospectively tested for hepatitis B surface antigen (HBsAg), and if positive, were tested for hepatitis B e antigen (HBeAg) at study entry and HBV viral load (VL) at delivery. Women who were HBsAg positive were classified as HIV-HBV co-infected (HIV-HBV). High HBV VL was defined as >10 6 IU/ml. The impact of HIV/HBV coinfection on HIV MTCT, low birth weight (LBW), infant mortality and maternal premature rupture of membranes and C-section was assessed using multivariate (MV) logistic and Cox regression. Results: Among 2025 HIV-infected (HIV) women, 88 (4.3%) were HIV-HBV. HIV-HBV women with high HBV VL had lower median CD4 T-cell count at study entry, when compared to HIV+/HBV- women or HIV-HBV women with HBV VL < 10 6 IU/ml (320, 490, and 434 cells/mm³, respectively (p<0.007)). In MV analysis, adjusted for maternal CD4, age, and maternal ART, infants born to women with high HBV VL were more likely to be low birth weight (LBW), compared to HIV+/ HBV- and HBV low VL women: [30% (3/10) vs 10% (194/1953) vs 6% (5/78), respectively, p=0.03)]. In a dose response analysis, HBV VL greater than 102 IU/ ML was associated with LBW [RR=6.1 (95% CI 1.31 - 28.39)]. HIV MTCT occurred in 2/10, 0/78, and 53/1953 high HBV VL, low HBV VL, and HIV+/HBV – women, respectively. High HBV VL was associated with HIV MTCT [(HR 6.75 (95% CI 1.86 – 24.50)]. There was no impact on infant mortality or maternal outcomes at 18 months. Conclusion: In HIV/HBV coinfected women, HBV replication increases the risk for poor infant outcomes including LBW and potentially HIV MTCT. Reduction of antepartum HBV viremia may have beneficial effects beyond the prevention of HBV MTCT in HIV/HBV coinfection. Robert Ntozini 1 , Jaya Chandna 1 , Ceri Evans 2 , Gwendoline Kandawasvika 3 , Bernard Chasekwa 1 , Florence D. Majo 1 , Naume Tavengwa 1 , Kuda Mutasa 1 , Batsirai Mutasa 1 , Lawrence Moulton 4 , Jean Humphrey 4 , Andrew Prendergast 2 , Melissa Gladstone 5 , for the SHINE Trial Team 1 Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe, 2 Queen Mary University of London, London, UK, 3 University of Zimbabwe, Harare, Zimbabwe, 4 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 5 University of Liverpool, Liverpool, UK Background: HIV-exposed children may be at risk of impaired early child development (ECD), but preventive interventions are currently limited. Methods: We conducted a 2x2 factorial cluster-randomized trial of improved infant and young child feeding (IYCF) and improved water, sanitation and hygiene (WASH) in rural Zimbabwe ( NCT01824940). Pregnant women were eligible if they lived in study clusters randomized to standard- of-care (SOC; 52 clusters); IYCF (20g Nutributter®/day for infants from 6-18mo, complementary feeding counseling; 53 clusters); WASH (pit latrine, 2 hand- washing stations, liquid soap, chlorine, play space, hygiene counseling; 53 clusters); or (IYCF+WASH; 53 clusters). A sub-study evaluated ECD outcomes at 2 years of age among HIV-exposed children using the Malawi Developmental Assessment Tool (MDAT; assessing motor, cognitive, language and social development); MacArthur-Bates Communication Development Inventory (CDI) (assessing vocabulary and grammar); A-not-B test (assessing object permanence); and a self-control task. Masking of participants/fieldworkers was not possible. Analysis was by intention-to-treat using unadjusted and adjusted generalized estimating equations. Results: 726 HIV-positive pregnant women were recruited. Mean (SD) CD4 count was 473 (221) cells/µL. Among 738 HIV-exposed live births (additional 12 from twin pregnancies), 323 children from 142 clusters had ECD assessments (68 from 31 SOC clusters; 68 from 40 IYCF clusters; 83 from 33 WASH clusters; 104 from 38 IYCF+WASH clusters). 300 children were HIV-exposed uninfected, 6 were HIV-positive and 17 had an unknown HIV status. Compared to SOC, children randomized to combined ICYF+WASH had higher MDAT scores (+4.6; 95%CI 1.9, 7.2), but there was no evidence of impact of IYCF or WASH alone (Table). The increase was accompanied by higher gross motor (+1.5; 95%CI 0.5, 2.5), fine motor (+0.7; 0.0, 1.5), language (+1.5; 95%CI 0.2, 2.8) and social components (+1.0; 95%CI 0.5, 1.5). Children randomized to combined

IYCF+WASH also had higher MacArthur-Bates CDI vocabulary scores (+8.5 words; 95%CI 3.7, 13.3), but we found no evidence of an impact of IYCF or WASH alone. There was no evidence of an impact of either intervention on object permanence or self-control. Conclusion: Combining IYCF and WASH interventions significantly improved motor and cognitive development in HIV-exposed children at 2 years of age.

Oral Abstracts

43 UNIQUE IMMUNOLOGICAL AND VIROLOGICAL FEATURES OF EARLY TREATED HIV-INFECTED NEWBORNS Pilar Garcia Broncano 1 , Kevin Einkauf 2 , Ce Gao 1 , Shivaali Maddali 1 , Chenyang Jiang 2 , Kenneth Maswabi 3 , Gbolahan Ajibola 3 , Sikhulile Moyo 3 , Terence Mohammed 3 , Thabani Ncube 3 , Joseph Makhema 3 , Kathleen M. Powis 4 , Daniel R. Kuritzkes 2 , Roger L. Shapiro 5 , Mathias Lichterfeld 2 1 Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA, 2 Brigham and Women’s Hospital, Boston, MA, USA, 3 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 4 Massachusetts General Hospital, Boston, MA, USA, 5 Harvard T.H. Chan School of Public Health, Boston, MA, USA Background: Studying HIV-1 infection in neonates with a developing immune systemmay offer unique opportunities for understanding viral reservoir establishment and exploring eradication strategies. The Early Infant Treatment (EIT) project in Botswana provides antiretroviral therapy (ART) to newborn HIV- 1-infected infants, and longitudinally evaluates virological and immunologic parameters. Methods: Serial PBMCs were collected from 10 infants with neonatal HIV-1 infection who started ART within 72 hours (n=9) or 31 days (n=1) after birth, and were followed for 84-96 weeks (w). PBMCs collected cross-sectionally in 10 infants after a median of 93w (range: 65-127) of ART started at a median of 119 days (range: 79-350) after birth were used as controls; PBMCs from HIV-1-negative infants (n=22) at 12w of life from Botswana were also analyzed. HIV-1 DNA was analyzed by near full-length single-genome sequencing, paired with corresponding chromosomal integration site analysis. Multiparametric flow cytometry was used to quantify phenotypic characteristics of innate and adaptive immune cells. Results: Compared with control children, EIT infants had lower total (5.3 vs 981.4, p<0.0001), intact (0.35 vs 2.4, p=0.006), and defective (1.9 vs 25.6, p=0.003) HIV-1 DNA copies/million PBMCs after 84-96w on ART. Intact proviral full-genomes represented an average of 54.3% of all sequences at baseline, compared with 5.9% at 84-96w on ART among EIT infants. Integration sites of 24 intact proviruses (determined at w0) were predominantly (71%) located in genes, with a preference for a configuration in the same orientation as host transcripts (65%); a similar distribution was noted for integration sites of defective proviruses. Proportions of mature CD56+CD16+ NK cells were significantly increased in EIT infants at 12w on ART relative to healthy infants (p=0.035); by contrast, the more immature CD56-CD16+ NK cells were notably reduced compared to controls (p=0.0031) and healthy infants (p=0.0006). HIV-1-specific CD8 T cells in EIT infants were weak in magnitude but displayed a polyfunctional profile. In a longitudinal analysis among EIT infants, positive correlations were found between total HIV-1 DNA copies and activated CD38+HLADR+ effector memory and terminally-differentiated CD8 T cells. Conclusion: Immediate initiation of ART during neonatal HIV-1 infection is associated with a remarkably reduced viral reservoir, a prematurely-expanded



CROI 2019

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