CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

Conclusion: The gut microbiota differs significantly at three months of age in bacterial composition and diversity by HIV infection and breastfeeding status, with higher α-diversity and differing β-diversity with HIV infection, and lower α-diversity and differing β-diversity with breastfeeding. The impact of these differences on systemic IF and IA in HIV+ infants requires further study.

but not in HIV-infected children. No significant differences were observed in the number of mtDNA mutations among the diverse groups of patients that were analyzed. Conclusion: Our results suggest that the mtDNA depletion in HIV-infected pregnant women and their HEU infants exposed to 1st generation NRTIs is not associated to increased mutagenesis. We observed no differences in mitochondrial parameters between patients exposed to 2nd generation NRTIs and healthy controls in either of the groups.

790 SURVIVING AND THRIVING? OUTCOMES OF HIV-EXPOSED CHILDREN IN RURAL ZIMBABWE Ceri Evans 1 , Bernard Chasekwa 2 , Robert Ntozini 2 , Florence D. Majo 2 , Kuda Mutasa 2 , Naume Tavengwa 2 , Batsirai Mutasa 2 , Mduduzi Mbuya 2 , Rebecca J. Stoltzfus 3 , Lawrence Moulton 4 , Jean Humphrey 4 , Andrew Prendergast 1 , for the SHINE Trial Team 1 Queen Mary University of London, London, UK, 2 Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe, 3 Cornell University, Ithaca, NY, USA, 4 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA Background: Prevention of mother-to-child transmission (PMTCT) programs have reduced the number of children acquiring HIV. However, the impact of PMTCT programs on mortality and growth of HIV-exposed children in sub- Saharan Africa is uncertain. Methods: SHINE was a community-based cluster-randomized trial of infant and young child feeding (IYCF) and water, sanitation and hygiene (WASH) interventions in two rural Zimbabwean districts with 15% HIV prevalence (ClinicalTrials.gov/NCT01824940). The trial did not administer PMTCT, but promoted early antenatal booking, uptake of PMTCT through local clinics, exclusive breastfeeding for 6 months, and prolonged breastfeeding to 24 months. Children were followed from birth and had longitudinal HIV testing. We used generalized estimating equations to compare mortality and growth between HIV-exposed and HIV-unexposed children through 18 months. Results: There were 738 HIV-exposed and 3989 HIV-unexposed live births between 2012-2015. 81% of HIV-positive mothers had documented ART use during pregnancy, and mean (SD) CD4 count was 473 (221) cells/μL. Overall, cumulative mortality in HIV-exposed children was 39% higher than HIV- unexposed children through 18 months (risk ratio 1.39; 95%CI 1.02, 1.89; P=0.04). 25 of 738 children (3%) were known to be HIV-infected by 18 months, 596 (81%) were HIV-exposed uninfected, and 117 (16%) children had an unknown HIV status. Among children confirmed to be HIV-exposed uninfected (HEU) at 18 months, mean length-for-age Z-score was -0.34 (95%CI -0.44, -0.25) lower than in HIV-unexposed children (P<0.001), and stunting prevalence was 46% versus 31% (risk ratio 1.48; 95%CI 1.34, 1.64; P<0.001). There were also significant differences between groups in weight-for-age, weight-for-height and head circumference; HEU children had almost 2-fold higher prevalence of underweight, wasting and microcephaly (Table). Among 738 HIV-exposed births, only 320 were known to be alive, HIV-free and non-stunted at 18 months. Conclusion: In the current PMTCT era, mortality and growth failure are higher among HIV-exposed compared to HIV-unexposed children in rural Zimbabwe; almost half of all HEU children were stunted by 18 months. As HIV transmission continues to decline, we propose the composite status of “Alive, HIV-free and non-stunted” as the long-term goal of PMTCT programs. Our findings highlight the ongoing poor outcomes of HEU children despite PMTCT, and the need for additional interventions to ensure that HIV-exposed children survive and thrive.

Poster Abstracts

789 COMPLETE MITOCHONDRIAL GENOME IN HIV-INFECTED CHILDREN AND MOTHER-CHILD PAIRS Claudia Fortuny 1 , Constanza Moren 2 , Lidia Carreño 3 , Elena Garcia-Arumí 3 , Emilia Sanchez 4 , Glòria Garrabou 2 , Ingrid Gonzalez-Casacuberta 2 , Ester Tobías 2 , Antoni Noguera-Julian 1 1 Hospital Sant Joan de Déu Barcelona, Esplugues, Spain, 2 Hospital Clinic of Barcelona, Barcelona, Spain, 3 Hospital Universitario de la Vall d’Hebron, Barcelona, Spain, 4 Universitat Ramon Llull, Barcelona, Spain Background: Antiretroviral therapy (ART) is universally recommended for HIV-infected children and HIV-infected pregnant women; HIV-exposed uninfected (HEU) infants are also exposed to ART during pregnancy. Current ART combinations include two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs); the association between the latter and mitochondrial DNA (mtDNA) depletion has been well documented. Whether mutational changes rely at the basis of such mtDNA depletion and whether 1st generation NRTIs (zidovudine, didanosine and stavudine) are more mutagenic than the rest of NRTIs (2nd generation: lamivudine/emtricitabine, tenofovir, abacavir) are questions that remain unclear. We aimed to assess the presence of mutations and depletion of mtDNA in 3 groups of patients exposed to either 1st or 2nd generation NRTIs: HIV-infected children, HIV-infected pregnant women and their HEU infants, and equivalent groups of HIV-uninfected ART-unexposed healthy controls. Methods: Cross-sectional study. Peripheral blood mononuclear cells (PBMC) were obtained simultaneously 6 weeks after birth from the mothers and their HEU infants and at a mean±SD age of 12.5±4.3 years in HIV-infected children. PBMCs were isolated through a Ficoll’s gradient. mtDNA depletion was determined through multiplex PCR (Applied Biosystems 7500 Real Time PCR System) in 96 well plates with the simultaneous determination of the mitochondrial 12S ribosomal RNA (mt12SrRNA) gene and the constitutive nuclear RNAseP gene (nRNAseP). To study heteroplasmic variants the whole mitochondrial genome was amplified by long range PCR. Sample libraries were prepared with Nextera XT kit (Illumina) and sequencing proceeded in the MiSeq. Row data were analyzed using MiSeq Reporter Software. Funded by ISCIII, Spain (PI13/01738). Results: None of the patients presented with clinical manifestations and/or analytical disorders consistent with mitochondrial dysfunction at assessment. MtDNA depletion was confirmed in HIV-infected mothers and their HEU infants,

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