Persistent HIV-1 infection in duodenal mucosa and memory CD8+ T cell differentiation Liliana Belmonte 1 PhD; Alberto Zalar 2 MD; Patricia Baré 1 PhD; Noel.

Slides:

Advertisements

Similar presentations

Purging the HIV-1 Reservoir Through the Disruption of the PD-1 Pathway

Advertisements

Assessment of residual HIV-1 viremia and persistent viral replication in highly suppressed patients: comparison of direct and indirect methods. B. Hernández-Novoa,

Markers of rapid HIV progression among untreated Argentinean seroconverters M.E. Socías, O. Sued, N. Laufer, H. Mingrone, C. Acuipil, E. Loiza, L. Amante,

Recommendations of BU/HIV expert panel influenced by results from Akonolinga All BU patients should be offered quality provider-initiated HIV testing and.

Interactive Workshop “HIV Cure 101”: Challenges in identifying and targeting the HIV reservoir Sarah Palmer Centre for Virus Research Westmead Millennium.

Instructions To use this template: –for each slide write the correct answer on the orange bar first –choose which option (A,B,C or D) and make sure you.

Controversies in HIV Cure Research Debate 1. Is there ongoing replication under HAART? Mario Stevenson and Frank Maldarelli Moderator: Steve Deeks.

Virologic and immunologic response following antiretroviral therapy initiation among pregnant and postpartum women with acute HIV-1 infection: MOPDB0101.

Marian Kerbleski, RN UCSF AIDS Division San Francisco General Hospital.

Role of Antiretroviral Therapy, Viral Replication, and HIV Infection in Atherosclerosis Priscilla Y. Hsue, Peter W. Hunt, Jeffrey N. Martin, Amanda Schnell,

Cell- and Tissue-based Measures of Viral Persistence Are Associated with Immune Activation and PD-1-Expressing CD4+ T cells H Hatano 1, V Jain 1, PW Hunt.

Detection of HIV-1 RNA in seminal plasma samples from treated patients with undetectable HIV-1 RNA in blood plasma Marcelin AG 1, Tubiana R 1, Lambert-Niclot.

DNA methylation as an epigenetic marker in HIV-2 disease in West Africa? Alberta Davis MRC Laboratories, Gambia 18th January 2013.

Persisting long term benefit of genotypic guided treatment in HIV infected patients failing HAART and Importance of Protease Inhibitor plasma levels. Viradapt.

Factors associated with a low HIV reservoir in patients with prolonged suppressive antiretroviral therapy S. Fourati 1, R. Calin 2, G. Carcelain 3, P.

Peter F. Rebeiro, PhD, MHS On behalf of: Carina Cesar, Bryan E. Shepherd, Raquel B. De Boni, Claudia Cortés, Fernanda Rodriguez, Pablo Belaunzarán-Zamudio,

Background There is uncertainty regarding the frequency, predictors, and outcomes of IRIS events Prior studies on IRIS have been limited to convenience.

HIV Cellular Pathogenesis III

Studies of HIV Eradication: a Case for Using NHP Models Guido Silvestri, MD Yerkes National Primate Research Center Emory University School of Medicine.

Detection of Immune Responses in Mucosal T-cells in Kenya Jackton Indangasi 2, Hannah Cheeseman 1, Onyango J. I. Obila 2, Simon Ogola 2, Robert Langat.

Transition Program of HIV-infected adolescents to Adult HIV care in Buenos Aires, Argentina S. Arazi Caillaud 1, D. Mecikovsky 1, A.Bordato.

Characterization of persistent HIV-1 in a broad spectrum of CD4 + T-cells isolated from peripheral blood, bone marrow, lymphoid tissue and gut associated.

1 Resistance and Tropism - Maraviroc Lisa K. Naeger, Ph.D. Division of Antiviral Products Food and Drug Administration April 24, 2007 FDA Antiviral Advisory.

Anti-HIV Antibody Responses Reflect the Quantifiable HIV Reservoir Size Sulggi Lee, M.D., Ph.D. Assistant Professor of Medicine University of California,

Impact of Raltegravir on Immune Reconstitution and Thymopoiesis in HIV-1 Infected Patients with Undetectable Viremia Carolina Garrido, N Rallón, N Zahonero,

INTRODUCTION Evaluation of Outcomes in Patients Starting Antiretroviral Therapy During Hospitalization Leigh E. Efird, PharmD 1, Manish Patel, PharmD 1,

Primary HIV-1 Infection Pathogenesis, Diagnosis, and Treatment Summary of Evidence Martin Markowitz M.D. Clinical Director and Staff Investigator Aaron.

Functional cure after long term HAART initiated during early HIV infection - a case study. van Lunzen J. 1,2, Schulze zur Wiesch J. 1,2, Schumacher U.

HBV related complications in HIV positive patients during HAART therapy Irina Magdalena Dumitru*, E. Dumitru*, S. Rugina*, Roxana Carmen Cernat**, Simona.

Learning About an HIV Cure by Doing Studies in HIV+ Subjects Alan Landay, PhD Professor and Chairman Department of Immunology/Microbiology Rush University.

Results Compliance with Breast Cancer Screening Guidelines in the HIV Clinic: A Quality Improvement Tool E. Patrozou M.D., E. Christaki M.D., L. Hicks.

HIV-1 infection decreases CD127 and PD1 expression on duodenal CD8+T cells Liliana Belmonte, PhD Academia Nacional de Medicina Buenos Aires, Argentina.

12th Conference on Retroviruses and Opportunistic Infections February 22-25, 2005 Boston, Massachusetts, USA Poster No. 830 Hematological Benefit of Switching.

High Discordance in Plasma and Genital Tract HIV-1 Drug Resistance in Indian Women Failing First-line Therapy MOPDA0106 S. Saravanan, PhD Session Code:

ImmunoPathogenesis of HIV Disease Overview of HIV Epidemic Basic biology of HIV-1 Stages of HIV Disease Viral and Cellular Dynamics after HAART HIV Therapy.

Evolution of the Functional Profile of HIV-Specific CD8+ T cells in a Cohort of Long Term Nonprogressors M López, N Rallón, A Peris, M Salgado, B Rodés,

Strategies for Management of Antiretroviral Therapy Study Wafaa El-Sadr and James Neaton for the SMART Study Team.

T-cell activation positively correlates with cell-associated HIV-DNA level in PBMCs in viremic patients with acute or chronic HIV-1 infection Laurence.

Treatment Failure HAIVN Harvard Medical School AIDS Initiative in Vietnam.

Phar. Nhat Mang/ Roche Vietnam

Immune reconstitution Anjie Zhen, PhD

Conclusions Materials and Methods Background Objectives HIV-1 RNA is the most significant determinant of cervical HIV-1 shedding. Shedding has also been.

Virology – Antivirals 2 JU- 2 nd Year Medical Students By Dr Hamed AlZoubi – Microbiology and Immunology Department – Mutah University. MBBS (J.U.S.T)

Response to Antiretroviral Treatment In an Ethiopian Hospital Samuel Hailemariam, MD, MPH; J Allen McCutchan, MD, MSc Meaza Demissie, MD, PMH, PHD; Alemayehu.

HAART Initiation Within 2 Weeks of Seroconversion Associated With Virologic and Immunologic Benefits Slideset on: Hecht FM, Wang L, Collier A, et al. A.

Mortality during the first year of HAART in HIV-1-infected patients in 7 countries from Latin America and the Caribbean Suely H. Tuboi, MD, PhD On behalf.

Background  HIV-1 infection persists in reservoirs and leads to progressive depletion of CD4+ T-cells even in subjects with slow disease progression 

The Dynamics of HIV RNA, CD4+ Count and Mycobacterium tuberculosis (Mtb) Antigen Specific Cytokines in TB/HIV Patients Following Successful Tuberculosis.

HIV Drug Resistance Surveillance Satellite Session: HIV Drug Resistance Surveillance and Control: a Global Concern Silvia Bertagnolio, MD WHO,

Adefovir Suppresses HBV DNA Levels in Lamivudine-Resistant HIV/HBV Patients Slideset on: Benhamou Y, Thibault V, Vig P, et al. Safety and efficacy of adefovir.

Expression Analysis of α4 integrin and related genetic polymorphisms in HIV acquisition and disease progression OF infected individuals Livia R. GóeS 1,

The impact of treatment duration on defective and expanded identical HIV genomes in T cell subsets from peripheral blood and tissues Eunok Lee.

Seroprevalence, prevalence, type and factors associated with HPV infection at multiple sites in young HIV-positive MSM On behalf of the HPV MAPS Research.

Emory University School of Medicine Department of Medicine

undetectable (undetectable-6.25)

Daniel Meressa, M.D. Global Health Committee St. Peter’s Hospital

IL-2 + IL-7, Scriptaid, Valproic acid, and Prostratin shows the most promise as a novel therapeutic regiment. Our ideal model that any new drug regimen.

Hospital de Pediatría “Prof. Dr. Juan P. Garrahan”.

Table 2. Mean intrasubject diversity for the 11 study participants, by genomic region. From: Hepatitis C Virus (HCV) Diversity in HIV-HCV-Coinfected Subjects.

Association of CD4+ T-lymphocyte counts and new thymic emigrants in HIV-infected children during successful highly active antiretroviral therapy Akihiko.

ADCC responses arising during acute/early HIV infection do not prevent rapid disease progression María Julia Ruiz 1, Yanina Ghiglione1, María Eugenia.

Galectin-9 binding to Tim-3 renders activated human CD4+ T cells less susceptible to HIV-1 infection by Shokrollah Elahi, Toshiro Niki, Mitsuomi Hirashima,

by Jason M. Brenchley, Mirko Paiardini, Kenneth S. Knox, Ava I

Immunodeficiency (2 of 2)

Brent E. Palmer, PhD, Douglas G. Mack, PhD, Allison K

Viral reservoirs, residual viremia, and the potential of highly active antiretroviral therapy to eradicate HIV infection Lin Shen, MD, Robert F. Siliciano,

Association of CD4+ T-lymphocyte counts and new thymic emigrants in HIV-infected children during successful highly active antiretroviral therapy Akihiko.

Keep control: Elite and post-treatment controllers

Rapid Detection of HIV-1 subtype C Integrase resistance mutations by the Use of High-Resolution Melting Analysis Tendai Washaya BSc, Msc. Pre-PhD Student.

INTRODUCTION OBJECTIVES METHODS RESULTS DISCUSSION

Presentation transcript:

Persistent HIV-1 infection in duodenal mucosa and memory CD8+ T cell differentiation Liliana Belmonte 1 PhD; Alberto Zalar 2 MD; Patricia Baré 1 PhD; Noel Badano 1 PhD st; Valentina Araya 2 MD; Eduardo Piskorz 2 MD; Maria Inés Figueroa 3 MD; Cecilia Parodi 1 PhD, Beatriz Ruibal-Ares 1 MD, Pedro Cahn 3 MD, PhD; Maria Marta de E de Bracco 1 PhD. Laboratory of Immunology and Virology 1, Academia Nacional de Medicina, Buenos Aires, Argentina. Gastroenterology 2 and Infectious Diseases 3 Units, Hospital Juan A Fernandez, Buenos Aires, Argentina.

Introduction Despite the clinical improvement associated with HAART, current antiviral drugs are not able to eradicate HIV due to the persistence of virus in tissue reservoirs. Viral reservoirs therefore represent a potentially life-long site of replication-competent forms of HIV that cannot be suppressed by current antiretroviral treatment

The objectives of the study were: ¤ To verify if HIV-1 persists in the intestine of HIV+ patients in spite of successful antiretroviral treatment (HAART) ¤ To identify the cells that harbour HIV-1 in the duodenal mucosa

Material and Methods A.- Distal duodenal biopsies were obtained from 13 patients with chronic HIV-1 infection under HAART: 9 males, 4 females, 9 males, 4 females, 7 with pVL < 50 copies/ml, Median CD4 cell count 354 cell/mm 3 (31-563) 7 with pVL < 50 copies/ml, Median CD4 cell count 354 cell/mm 3 (31-563) 6 with pVL> copies/ml, Median CD4 cell count 58 cell/mm 3 (7-198) 6 with pVL> copies/ml, Median CD4 cell count 58 cell/mm 3 (7-198) Distal duodenal biopsies from 10 HIV-1 seronegative individuals were used as control (C). B.- A biopsy was labeled as “HIV +” if HIV-DNA was detected by standard PCR (using primers SK145 and SKCC1B to define a sequence of 155 nucleotides within the highly conserved region of the HIV-1 gag gene) C.- The phenotype of leukocytes present in the tissue was assessed by flow cytometry using anti CD4, CD64, CD27, CD28, CD45RO. HIV-1 detection was performed by intracellular staining with KC57 antibody (anti-p24).

CD4 depletion in duodenal mucosa n:13 n:10

CD8+ T cells in duodenal mucosa n:13 n:10

Characteristics of duodenal CD8+ T cell population p=0.001 p=0.027 % % % % % p=NS

Patients ND pVL (n=7) Patients pVL > copies/ml (n=6) HIV + Biopsies 44 HIV- Biopsies Biopsies32 Lack of correlation of pVL with HIV persistence in duodenal mucosa p=0.72, chi-square test

p24 positivity in duodenal CD64+ cells Control Biopsy HIV- biopsy (by PCR) HIV+ biopsy (by PCR) Control isotype p24 expression KC57 FITC Median FI KC57: 193 Median FI isotype: 52 Median FI KC57: 56 Median FI isotype: 47 Median FI KC57: 45 Median FI isotype: 35

p24 positivity in duodenal CD68+ Macrophages HIV+ biopsy (by PCR) Control Biopsy Control isotype p24 expression Median FI KC57: 158 Median FI isotype: 54 Median FI KC57: 67 Median FI isotype: 57

Conclusions  As reported in other segments of the GI tract, we found that CD4 T cells were depleted in duodenal mucosa of HIV patients when compared to controls, while no differences were observed in the proportion of CD8 T cells in both groups.  However, the persistence of HIV in the duodenal tissue affects the differentiation pattern of CD8 T cells. Thus, the proportion of fully differentiated CD8+ T cells was higher in the absence of HIV in the duodenum of HIV patients.

Conclusions  HIV-DNA could be detected in the duodenal mucosa both in patients who failed treatment and in those with undetectable pVL.  Concerning the nature of cells that harbour HIV infection, we have shown that macrophages may host persistent HIV infection and could be considered as a reservoir of HIV even after HAART.