CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

46% of mothers had health issues or serious life events but no mortality. 12 (9%) of infants died, 7 (5%) progressed to stage 3 or 4, and 16 (12%) had CD4 <25%. In total, 32 (24%) had poor outcomes. Only 34 (25%) infants suppressed VL during follow-up at a median time of 5.2 months. According to the model, determinants of poor outcome were VL and age at ART, after adjustment by site, baseline WAZ and ART regimen. The hazard of poor outcome was almost 3X higher (HR: 2.7 [1.3-5.8], p=0.010) per each VL log persistently elevated during the follow-up, and 50% higher for every month that ART was delayed (HR: 1.5 [1.01-2.2], p=0.049). At this point, time to suppression was influenced only by baseline VL (HR: 0.01 [0.002-0.1], p<0.001) and maternal severe life events/ health issues (HR: 0.4 [0.8-0.9], p=0.042). Conclusion: Despite early ART, a high proportion of infants have a poor outcome during the first months of life. The poor outcome is mainly influenced by VL during follow-up and age at ART initiation

1 University of California Los Angeles, Los Angeles, CA, USA, 2 Columbia University Medical Center, New York, NY, USA Background: HIV-exposed, uninfected (HEU) infants experience almost twice the morbidity and mortality of their HIV-unexposed uninfected (HUU) counterparts. The mechanisms by which maternal HIV-infection alters infant immune development are under investigation. Maternal HIV infection is associated with alterations of breast milk human milk oligosaccharide (HMO) composition and the gut microbiome of HEU infants. Whether perturbations in maternal HMO composition in HIV-infected mothers alter the infant gut microbiome or whether infant gut microbial populations and maternal HMO profile are correlated for other reasons remains unknown. Methods: 50 maternal-infant pairs were enrolled, half with maternal HIV, in a cross-sectional study at 1-3 months postpartum. 17 HEU and 25 HUU had stool shotgun metagenomics performed and maternal breast milk HMO data available. Host DNA removal followed by taxonomic classification using kraken v2.0 against the NCBI database resulted in 14.5 million reads assigned to 3720 taxa. 17 unique HMO isoforms were quantified using high-performance liquid chromatography. Statistical tests were performed in the R environment, v. 3.5.2. Results: Alpha diversity tended to be lower in HEU compared to HUU infants. In contrast, maternal HMO alpha diversity tended to be increased in HIV-positive compared to HIV-negative mothers. In HEU infants, negative correlations were observed between Bifidobacterium breve and LNnT, Bacteroides vulgatus and LNFP III, Bacteroides fragilis and several other HMO including 2’FL, 3’SL, DSLNT, FLNH, LNFP I, as well as total HMO concentration. Escherichia coli was negatively correlated with DFLNH, DSLNT, and LNFP I, but had a positive correlation with LNFP II (FDR-adjusted p < 0.1). In HUU infants, the correlations were different: Bifidobacterium bifidumwas negatively correlated with DFLNH, B. breve was negatively correlated with LNnT and LSTc, and Bacteroides fragilis was positively correlated with LSTb (p < 0.1). Correlations of pathways assessed by HUMAnN2 were found between chorismite biosynthesis I (found in B. fragilis and Akkermansia municiphila) and L-ornithine (found in B. breve and Bifidobacterium longum) and 3’FL, 3’SL, and DFLNT (p < 0.1). Conclusion: Maternal HIV status modulates the associations between HMO profile and infant microbiota. These differential correlations suggest that bacterial utilization of HMO differs in HEU infants which may, in turn, contribute to altered GI and immune development and increased mortality of HEU infants. 806 POOR OUTCOME IN EARLY TREATED HIV PERINATALLY INFECTED INFANTS IN AFRICA Alfredo Tagarro 1 , Sara Dominguez Rodriguez 1 , Avy Violari 2 , Mark Cotton 3 , Tacilta Mhampossa 4 , Nigel Klein 5 , Nastassja Ramsagar 2 , Anita Janse Van Rensburg 3 , Osse Behuhuma 5 , Paula Vaz 6 , Andrea Oletto 7 , Paolo Palma 8 , Paolo Rossi 8 , Pablo Rojo Conejo 1 , for the EPIICAL Consortium 1 Hospital Universitario 12 de Octubre, Madrid, Spain, 2 Perinatal HIV Research Unit, Soweto, South Africa, 3 Tygerberg Hospital, Cape Town, South Africa, 4 Centro de Investigaçao em Saude de Manhiça, Maputo, Mozambique, 5 Africa Health Research Institute, Mtubatuba, South Africa, 6 Fundação Ariel Glaser Contra o SIDA Pediátrico, Maputo, Mozambique, 7 Penta Foundation, Padova, Italy, 8 Bambino Gesu Children's Hospital, Rome, Italy Background: HIV-infected infants should be treated early after diagnosis. Mortality and morbidity peak in the first 6 months after ART initiation and in infants < 1-year-old. Mortality is linked to advanced disease at diagnosis. There are few data about determinants of poor outcome in early-treated infants. The aim is to assess risk factors for poor outcome despite early ART in a cohort of infants in South Africa and Mozambique. Methods: EARTH is a multi-centre cohort enrolling HIV-infected infants diagnosed and treated in the first 3 months of life. Enrolment started in May 2018. ART regimens followed national guidelines. Poor outcome was defined as mortality or severe disease (progression to WHO clinical stage 3 or 4 or CD4 below 25%). Risk factors for poor outcome and viral load (VL) suppression adjusting for socio-demographics, clinical, immunological and virological measures were assessed by multivariable time-dependent Cox-proportional hazards model, including time-dependent coefficient for follow-up VL and CD4. Results: To date, 135 infants were enrolled. Currently, the median follow-up time is 5.5 months (IQR 2.7-6.9). Median age at enrolment was 38 days (31-75), and median age at ART was 33 days (19-66). Fifty-four percent were male, 37% were premature and 30% had baseline weight-for-age Z-Score (WAZ) <-2SD. Prophylaxis after birth was prescribed to 80%. Median baseline VL was 5.1 logs (3.6-6.1). Median baseline CD4 was 35% (26.3-44.4). During the follow-up,

Poster Abstracts

807 VIRAL RESPONSE IN HIV-INFECTED INFANTS STARTING ART AT 1 MONTH IN SOUTHERN MOZAMBIQUE Maria G. Lain 1 , Paula Vaz 1 , Nalia Ismael 2 , Anna Cantarutti 3 , Gloria Porcu 3 , Paolo Palma 4 , Nicola Cotugno 4 , Dulce Bila 1 , Stefano Rinaldi 5 , Suresh Pallikkuth 5 , Rajendra Pahwa 5 , Elsa Taibo 1 , Esmeralda Karajeanes 1 , Carlo Giaquinto 6 , Savita Pahwa 5 1 Fundação Ariel Glaser Contra o SIDA Pediátrico, Maputo, Mozambique, 2 Instituto Nacional de Saúde, Maputo, Mozambique, 3 University of Milano, Milano, Italy, 4 Bambino Gesu Children's Hospital, Rome, Italy, 5 University of Miami, Miami, FL, USA, 6 University of Padova, Padova, Italy Background: In perinatal HIV infection, early infant HIV diagnosis and initiation of antiretroviral treatment (ART) are critical for achievement of viral suppression and long-term remission into childhood and adolescence. This study was aimed at investigating viral response of a cohort of infants who started ART in the first month of life in southern Mozambique. Methods: Project TARA (Towards AIDS Remission Approaches) included a descriptive cohort study of HIV perinatally infected infants who started ART at <2mo of age and were followed with frequent plasma virus load (VL) measures for two years under a NIH funded grant. VL monitoring was performed at 1, 2, 4, 5, 8, 9, 11, 17, 18 and 23mo and those with >4 measurements were included in the analysis. Kaplan–Meier estimator and descriptive analyses were used to summarize infants virologic response. Results: Thirty infants started ART with ZDV/3TC/LPVr at 34 days (IQR 18). Median pre-ART VL was 1.988.708c/ml (IQR 4.661.355). 18/30 (60%) reached viral suppression (VS), defined as HIV RNA plasma < 1000copies/ml, within a median time of 7.86mo (1-24mo) after ART initiation. 9/18 (50%) infants who initially achieved VS had a rebound within 3.3 mo (1-10mo); 5/9 re-suppressed within 3mo (1-7mo). 14/30 (47%) infants had sustained VS defined as ≥ 2 consecutive VS measures. Cumulative probability of VS among all infants was 43% at 6mo, 56% at 12mo and 73% at 18mo (Fig1). Among 18 infants adherent to ART who reached VLS, the median time to control the virus was 3mo (0.92-16.41mo); at 12mo the probability of VS was 89%. There was no statistically significant difference in time to VS among infants with pre-ART VL>Log6 compared to those with VL

CROI 2020 299