Supported by: NIAID/NHLBI R24 AI067039, NIAID R21 AI087360 Viremia copy-years: A measure of cumulative HIV burden among patients initiating antiretroviral.

Slides:

Advertisements

Similar presentations

DACS 272 Neurologic deficits in the years following ART initiation among subjects in the AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized.

Advertisements

A Prognostic Index for those Aging with HIV: Extension of the VACS Index to those on Combination Anti-Retroviral Therapy (cART) AC Justice* 1,2, S Modur.

Slide 1 of 11 From CB Hicks, MD, at Chicago, IL: May 20, 2013, IAS-USA. IAS–USA Charles B. Hicks, MD Professor of Medicine Duke University Medical Center.

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

Protective HLA Class I alleles are associated with reduced immune activation in Primary HIV infection Elizabeth Hamlyn 1, Stephen Hickling 2, Abdel Babiker.

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

HIV Early Treatment Project Groups 1 and 2 n Among HIV-infected participants in sub-Saharan Africa, does initiation of antiretroviral treatment (ART) at.

Patients in routine HIV clinical care at-risk for potentially transmitting HIV in the “test and treat” era of HIV prevention Crane, HM, Mimiaga, M, Feldman,

Introduction DCDOH supports HIV test and treat activities - increased number of HIV tests performed, emphasis on earlier linkage to care. Limited data.

Is monitoring for CD4 counts still needed for the management of patients with long- term HIV RNA suppression? Andrew Hill, Liverpool University, UK.

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

Phylogenetic Insight into HIV Transmission Networks in a Southeastern US Cohort Ann Dennis 1, Stéphane Hué 2, Christopher Hurt 1, Sonia Napravnik 1, Deenan.

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

Increased clinical events in HIV-infected patients who achieve full virologic suppression but fail to attain a CD4 count ≥ 200 cells/mm 3 after one year.

The Immunologic Efficacy of Antiretroviral Therapy among HIV-infected Patients in North America and Africa Elvin Geng* 1, Eric Vittinghoff 1, Jean Nachega.

Catherine Kober Margaret Johnson Martin Fisher Caroline Sabin On behalf of UK-CHIC BHIVA/BASHH Manchester 2010 Non-uptake of HAART among patients with.

Management and Development for Health (MDH)

Impact of HSV-2 suppressive therapy with daily acyclovir on HIV-1 disease progression: a randomized placebo- controlled trial in Rakai, Uganda Steven J.

Background Acknowledgements: Support was provided by NIAID grants U01 AI042170, U01 AI and U01 AI (CPCRA & INSIGHT) and R44AI (NIAID.

Impact of Highly Active Antiretroviral Therapy on the Incidence of HIV- encephalopathy among perinatally- infected children and adolescents. Kunjal Patel,

Life expectancy of patients treated with ART in the UK: UK CHIC Study Margaret May University of Bristol, Department of Social Medicine, Bristol.

Neurocognitive Impairment in HIV-Infected Subjects on HAART: Prevalence and Associations Kevin Robertson *1, Kunling Wu 2, Thomas Parsons 1, Ron Ellis.

The Positive Predictive Value of World Health Organization (WHO) Immunologic Criteria for Treatment Failure in a Public Health Antiretroviral Delivery.

Arnold School of Public Health Health Services, Policy, and Management 1 Drug Treatment Disparities Among African Americans Living with HIV/AIDS Carleen.

Introductory talk D Costagliola.

Switch to LPV/r monotherapy  Pilot LPV/r  M  LPV/r Mono  KalMo  OK  OK04  KALESOLO  MOST  HIV-NAT 077.

Immune Discordance on Highly Active Antiretroviral Therapy Can Still be Regarded as a Therapeutic Success Nur F. Önen MD, MRCP 1, Rachel Presti MD PhD.

Lipoatrophy and lipohypertrophy are independently associated with hypertension: the effect of lipoatrophy but not lipohypertrophy on hypertension is independent.

Good Three-year Outcomes of Antiretroviral Therapy at Multiple NGO- assisted facilities in Four Provinces in South Africa Geoffrey Fatti, Ashraf Grimwood.

The effect of tuberculosis treatment on virologic and immunologic response to combination antiretroviral therapy among South African children Heidi M.

Progressive histological liver improvement after sustained virological response to therapy in HCV / HIV coinfected patients. Jose L. Casado,

Persistent immune activation despite suppressive HAART is associated with higher risk for viral blips in HIV-1 infected individuals Alexander Zoufaly 1.

02-15 INFC Substitution of raltegravir for ritonavir-boosted protease inhibitors in HIV-infected patients: The SPIRAL study* 1 Date of preparation:

INTRODUCTION A previous cohort study from our unit suggested a benefit for the use of efavirenz compared to nevirapine in a group of patients initiating.

Evaluation of the WHO immunologic criteria for treatment failure among adults on first-line HAART in south India Snigdha Vallabhaneni 1, Sara Chandy 2,

Outcomes of Antiretroviral Treatment Programs in Rural Lesotho: Health Centers and Hospitals Compared Niklaus Labhardt, Motlalepula Sello, Mamokone A.

Outcomes in ART treatment programmes with and without access to routine viral load monitoring Olivia Keiser on behalf of IeDEA Southern Africa

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.

Accumulation of Protease Mutations Among Patients on Non-Suppressive 2 nd -Line ART in Nigeria H. Rawizza, B. Chaplin, S. Meloni, P. Okonkwo, P. Kanki.

The Impact of Darunavir/ritonavir (DRV/r) & Raltegravir (RAL) in the Clinic: A New Era for Treatment-Experienced Patients? M. Mugavero 1, H. Lin 1, J.

Long-Term Comparison of Nevirapine Versus Efavirenz When Combined with Other Antiretroviral Drugs in HIV-1 Positive Antiretroviral-Naïve Persons- The NNRTI.

Figure 2: Trends in currently prescribed antiretroviral therapy % prescribed HAART increased from 74% to 83% Trends in ART use, HIV viral load, and CD4.

Cumulative plasma HIV-1 level as a novel tool to evaluate antiretroviral therapy efficacy at the individual and public health levels Presented by Viviane.

Weekly Alendronate Safe and Effective at Increasing Bone Mineral Density in HIV-Infected Persons on Antiretroviral Therapy Slideset on: McComsey GA, Kendall.

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.

CD4 trajectory among HIV positive patients receiving HAART in a large East African HIV care centre Agnes N. Kiragga 1, Beverly Musick 2 Ronald Bosch, Ann.

Date of download: 6/3/2016 From: U.S. Trends in Antiretroviral Therapy Use, HIV RNA Plasma Viral Loads, and CD4 T-Lymphocyte Cell Counts Among HIV-Infected.

Efavirenz Use Not Associated With Depressive Episodes, According to Analysis of Randomized Clinical Trial Outcomes Slideset on: Journot V, Chene G, De.

1 Meet the Author Webinar March 15, Ground Rules for Webinar Participation Actively participate and write your questions into the chat area during.

HIV co-receptor tropism in treatment-naïve patients: impact on CD4 decline and subsequent response to HAART Laura Waters, Sundhiya Mandalia, Adrian Wildfire,

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.

Date of download: 7/6/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Effect of Antiretroviral Therapy on Viral Load, CD4.

First-Line Treatment of HIV Infection With Either NNRTI- or PI-Based Regimens Effective for Long-term Disease Control Slideset on: MacArthur RD, Novak.

Tipranavir/Ritonavir Superior to Comparator PI/Ritonavir at Week 48 in Multiclass-Experienced Patients Slideset on: Hicks CB, Cahn P, Cooper DA, et al.

ARV-trial.com Switch to TDF/FTC/EFV AI Study 1.

Earlier treatment and lower mortality in infants Initiating ART at

Lopinavir-ritonavir mg BID (n = 354)

Validating Definitions of Antiretroviral Treatment Failure in Malawi

Better Retention Rates Observed in Patients on Lopinavir than Atazanavir in Uganda

Juan Gonzalez Perez AIDS Healthcare Foundation

Immune activation set point during early HIV infection predicts subsequent CD4+ T-cell changes independent of viral load by Steven G. Deeks, Christina.

Syndemics Predict Bio-Behavioral HIV Sexual Transmission Risk Behavior Longitudinally in US HIV Clinics Satyanand Satyanarayana, Steven A. Safren, Brooke.

Long-Term Clinical and Immunologic Outcomes Are Similar in HIV-Infected Persons Randomized to NNRTI versus PI versus NNRTI+PI-based Antiretroviral Regimens.

Shawn L Fultz, MD MPH VACS Scientific Meeting, Feb 2004

Melissa Herrin, Jan Tate ScD, MPH & Amy Justice, MD, PhD

ARV-trial.com Switch to TDF/FTC/EFV AI Study 1.

Switch to LPV/r monotherapy

Public Health Implications

Presentation transcript:

Supported by: NIAID/NHLBI R24 AI067039, NIAID R21 AI Viremia copy-years: A measure of cumulative HIV burden among patients initiating antiretroviral therapy predicts long-term clinical outcomes Michael Mugavero 1, Sonia Napravnik 2, Stephen Cole 2, Joseph Eron 2, Bryan Lau 3, Heidi Crane 4, James Willig 1, Mari Kitahata 4, Michael Saag 1, and CFAR Network of Integrated Clinical Systems (CNICS) 1 University of Alabama at Birmingham, 2 University of North Carolina at Chapel Hill, 3 Johns Hopkins University, and 4 University of Washington

Supported by: NIAID/NHLBI R24 AI067039, NIAID R21 AI Background Single plasma HIV viral load (VL) on combination antiretroviral therapy (cART) predicts clinical outcomes (Egger M et al. Lancet 2002;360:119-29, Chene G et al. Lancet 2003;362:679-86, Lanoy E et al. AIDS 2009;23: ) But a single VL value cannot capture effects of intermittent viral replication over time Therefore, we developed viremia copy-years (VCY) to capture longitudinal cumulative VL burden

Supported by: NIAID/NHLBI R24 AI067039, NIAID R21 AI087360

Viremia Copy-Years Estimate of cumulative HIV burden over time Example: 10,000 copy-years  1,000 c/mL per day for 10 years  10,000 c/mL per day for 1 year VCY approximated as time-weighted sum using trapezoidal rule: Cole SR et al. Am J Epidemiology 2010;171:

Supported by: NIAID/NHLBI R24 AI067039, NIAID R21 AI Aims Evaluate patient factors associated with VCY following modern cART initiation Estimate the prognostic value of VCY following modern cART initiation

Supported by: NIAID/NHLBI R24 AI067039, NIAID R21 AI Methods Cohort: CNICS  8-site US clinical cohort  Kitahata et al., Int J Epi : Eligibility Criteria  ART-naïve initiating therapy  Initiated with modern cART  PI/r or NNRTI-based regimen  At least 12 months f/u from cART start Principal exposure: Viremia Copy-Years (VCY)

Supported by: NIAID/NHLBI R24 AI067039, NIAID R21 AI Methods Relationships between patient factors and VCY  Multivariable linear regression of log 10 VCY with robust variances Relationship between log 10 VCY and all- cause mortality  Cox proportional hazards models

Supported by: NIAID/NHLBI R24 AI067039, NIAID R21 AI Results: Study Population Characteristic (N=1906)N (%) or Median (IQR) Female381 (20%) Black724 (38%) Ritonavir-boosted PI591 (31%) Pre-cART CD4 cell count, cells/mm (55, 282) Pre-cART log 10 VL, copies/mL4.9 (4.4, 5.4) Follow-up, years3.5 (2.0, 5.4) VL measures contributed (n=24,105)11 (6, 17) VCY, log 10 copy-years/mL2.76 (2.21, 3.89) VCY, copy-years/mL575 (162, 7762)

Supported by: NIAID/NHLBI R24 AI067039, NIAID R21 AI Results: Relationship between patient factors and VCY from modern cART initiation Patient Factorslog 10 VCY a 95% CIP value CD4 at cART-initiation (per 100 cell increase) , -0.03<0.01 Women , 0.63<0.01 Ritonavir-boosted PI b , 0.50<0.01 a Multivariable linear regression model controlling for CD4 at cART initiation, sex, initial cART, duration of treatment and site. b Measured at cART-initiation, comparison group are patients initiating an NNRTI- based regimen, intention to treat approach * Higher pre-cART VL was associated with greater VCY in bivariable but not multivariable models

Supported by: NIAID/NHLBI R24 AI067039, NIAID R21 AI Results: Relationship between VCY and all- cause mortality from modern cART initiation a Multivariable Cox proportional hazards model controlling for pre-cART VL, peak VL, time-updated VL, time-updated CD4, age, sex, initial cART (cART switches / discontinuations were not included), HIV acquisition mode, and site Hazard Ratio a 95% CIP value VCY, log 10 copy-years/mL , Pre-cART VL, log 10 copies/mL , Peak VL on cART, log 10 copies/mL , Time-updated VL, log 10 copies/mL , Time-updated CD4 (per 100 cell increase) , 0.85<0.01

Supported by: NIAID/NHLBI R24 AI067039, NIAID R21 AI Conclusions VCY, an estimate of cumulative HIV burden, was associated with several patient characteristics following cART-initiation  Independent of cross-sectional VL and CD4 cell count  Among patients initiating modern cART regimens VCY had demonstrable prognostic value for all-cause mortality  Independent of cross-sectional and time-updated VL and CD4 measures, and other patient factors

Supported by: NIAID/NHLBI R24 AI067039, NIAID R21 AI Conclusions Future studies of VCY will include:  Evaluating the effect of VCY on clinical outcomes among specific groups of patients, including those with low- level or intermittent viremia  Estimating the relationship between VCY and AIDS- and non-AIDS events  Assessing relationships between VCY and markers of inflammation and immune activation

Supported by: NIAID/NHLBI R24 AI067039, NIAID R21 AI Acknowledgements Co-authors CNICS patients CNICS site PIs & co-investigators Stephen Van Rompaey Donna Porter CNICS site staff