CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

IA(CD4+HLA-DR+CD38+<7%; CD8+HLA-DR+CD38+<18%); the second(n=120) by high CD4 percentage, P-selectin and thrombomodulin; the third(n=11) by high levels of DR+ and Ki-67+; & the fourth(n=13) by unsuppressed HIV(50%), high Interleukin-6 and Tumour Necrosis Factor-α. Specific and broad-range PCRs for bacterial DNA were negative/ very low in all groups, and across all clusters. At baseline using NGS, very low levels of microbial DNA were found in both HIV infected groups, including Staphylococcus aureus, Enterobacteriaceae, Veillonellae & Clostridiales. Levels of microbial DNA did not differ between clusters except Enterobacteriaceae(higher in clusters 1 & 3 compared to cluster 2 & 4(p<0.01)). Conclusion: IA decreased over time on ART, with clustering of IA markers indicating different IA patterns by HIV/ART status and viral load suppression. Levels of bacterial DNA were low regardless of HIV/ART/IA status or duration of ART. MT does not appear to be a significant driver of IA in this setting.

Poster and Themed Discussion Abstracts

802 TARGETING IMMUNOACTIVATION IN HIV+ CHILDREN BY MODIFICATION OF THE GUT MICROBIOTA Talía Sainz 1 , Nuria Jiménez-Hernández 2 , Laura Diaz 3 , Sergio Serrano-Villar 4 , Maria José Mellado 1 , Luis Prieto 5 , Jose Tomas Ramos 6 , M. Ángeles Muñoz-Fernández 3 , María José Gosalbes 2 , Maria Luisa Navarro 3 1 Hosp La Paz Inst for Hlth Rsr, Madrid, Spain, 2 FISABIO–Salud Pública, Valencia, Spain, 3 Gregorio Maranon Hosp, Madrid, Spain, 4 Hosp Univ Ramón y Cajal, Madrid, Spain, 5 Hosp de Getafe, Madrid, Spain, 6 Hosp Clínico San Carlos, Madrid, Spain Background: Dysbiosis of the microbial gut appears to contribute chronic bacterial translocation and systemic inflammation in HIV-infected adults on antiretroviral therapy (ART). We aimed to modulate the intestinal microbiota of vertically HIV-infected children using a nutritional supplement, and to assess the impact on immunoactivation. Methods: Pilot, double blind, randomized placebo-controlled trial including HIV-infected children receiving a symbiotic nutritional supplement. DNA was extracted at baseline and after a 4-week intervention from stool samples and 16S rRNA gene amplicons were pyrosequenced. Activated (CD38+HLADR+), senescent (CD57+CD28-), regulatory (CD4+/ FoxP3+) and naive (CCR7+/CD45RA+)/memory T-cell subsets were determined using flow cytometry and analyzed using Wilcoxon matched pairs test. Uninfected siblings were recruited as controls for characterization of the microbiota in HIV-infected children. Results: Twenty-two vertically HIV-infected children were recruited and compared to 11 controls. Mean age was 11.4±3.4 years and 8 (32%) were males. All were on ART and had HIV RNA<50/ml. At baseline, their microbiota showed reduced alpha diversity compared to controls (P=0.042) and distinct composition at the genus level (Unifrac distances, Adonis P=0.042). After the intervention, changes in overall microbiota structure between cases and controls were non-significant, and a significant increase of the butyrate producers Faecalibacterium and Butyricicoccus was documented. No significant changes in total CD4 counts or CD4/CD8 ratio was observed after intervention. Changes in the frequency of activated, senescent, regulatory and/or naive/memory T cells were all non-significant. Conclusion: In this pilot study we observed that vertical HIV infection alters the fecal microbiota structure in children. A short symbiotic nutritional intervention increased the abundance of butyrate producing bacteria, generally indicative of a healthy gut-microbiota homeostasis although did not elicit detectable effects in peripheral T cell markers. The potential anti-inflammatory effect of targeting the microbiota early in life in HIV disease deserves further investigation.

CROI 2017 347