THE BODY PRO The HIV Resource for Health Professionals Faculty: Benjamin Young, M.D., Ph.D. Assistant Clinical Professor of Medicine at the University

THE BODY PROThe HIV Resource for Health Professionals

Faculty: Benjamin Young, M.D., Ph.D. Assistant Clinical Professor of Medicine at theUniversity of Colorado

The Body PRO Covers ICAAC/IDSA 2008Washington, D.C.; October 25-28, 2008

Copyright © 2008 The HealthCentral Network, Inc. All rights reserved.

This activity is jointly sponsored by Postgraduate Institute for Medicine and The Body PRO.

Benjamin Young, M.D., Ph.D.

Reappraising Key Issues in HIV Clinical Management:Highlights From ICAAC/IDSA 2008

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Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008

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Faculty for This ActivityFaculty for This Activity

Benjamin Young, M.D., Ph.D.

Benjamin Young, M.D., Ph.D. is assistant clinical professor of medicine at the University of Colorado and consultant physician for Denver ID Consultants at Rose Medical Center in Denver.

Dr. Young is the author of numerous journal articles, reviews and studies relating to HIV and its treatment. He is a principal investigator with the HIV Outpatient Study, a massive ongoing analysis of the health of HIV-positive people throughout the U.S. A member of the HIV Medicine Association and the American Academy of HIV Medicine, Dr. Young is also actively involved in educating health care professionals and community groups throughout the world on HIV-related subjects. He has devoted the past two years to training HIV physicians in Eastern Europe and Central Asia.

DisclosuresDr. Young has been a consultant for Bristol-Myers Squibb, Cerner Corporation, Gilead Sciences, GlaxoSmithKline, Hoffmann-La Roche, Inc., Merck & Co., Monogram Biosciences and Pfizer, Inc. He has served on speaker bureaus for Gilead Sciences, GlaxoSmithKline, Merck and Monogram. In addition, he has received research support from Bristol-Myers Squibb, Cerner Corporation, Gilead Sciences, GlaxoSmithKline, Hoffman-La Roche and Merck.

This activity is supported by an educational grant from

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3HOPS: Incidence of High Frequency Infectious Opportunistic Infections, 1994 – 2006

HOPS: Incidence of High Frequency Infectious Opportunistic Infections, 1994 – 2006

JT Brooks et al. ICAAC/IDSA 2008; abstract H-2330. Reprinted with permission.

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HOPS: Incidence Rates of Malignant Opportunistic Infections, 1994 – 2006HOPS: Incidence Rates of Malignant Opportunistic Infections, 1994 – 2006


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5HOPS: Median CD4+ Cell Counts at Opportunistic Infection Diagnosis, 1994 – 2006

HOPS: Median CD4+ Cell Counts at Opportunistic Infection Diagnosis, 1994 – 2006


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DUET: Study Design and Major Inclusion CriteriaDUET: Study Design and Major Inclusion Criteria

Richard Haubrich et al. ICAAC/IDSA 2008; abstract H-1239. Reprinted with permission.

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DUET: Proportion of Patients With Any ADE or DeathDUET: Proportion of Patients With Any ADE or Death


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DUET: Proportion of Patients Hospitalized by Week 48*DUET: Proportion of Patients Hospitalized by Week 48*


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DUET: Cumulative Hospital Days Over 48 WeeksDUET: Cumulative Hospital Days Over 48 Weeks


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BENCHMRK 1 & 2: Study DesignBENCHMRK 1 & 2: Study Design

• Randomized, double-blind, placebo-controlled with Data and Safety Monitoring Board

• Primary analysis at Week 16; secondary analysis at Week 48

Raltegravir 400 mg BID + OBTP018* (n = 234)P019* (n = 232)

Placebo + OBTP018* (n = 118)P019* (n = 119)

HIV-1-infectedTriple-class resistant

HIV-1 RNA > 1,000 copies/mLNo CD4 cell cut-off

Protocol 018* (n = 352)Europe, Asia/Pacific and Peru

Protocol 019* (n = 351)North and South America

2:1

• OBT was selected by investigator based on baseline resistance testing and prior treatment history. Selected investigational ARTs, darunavir and tipranavir, were permitted.

*Protocol 018 (P018) is BENCHMRK-1; Protocol 019 (P019) is BENCHMRK-2

Primary EndpointsWeek 16

Planned DurationWeek 240

Joseph Eron et al. ICAAC/IDSA 2008; abstract H-1249. Reprinted with permission.Copyright © 2008 Merck & Co., Inc., Whitehouse Stations, New Jersey, USA, All Rights Reserved.

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11BENCHMRK 1 & 2: Time to First AIDS-Defining Condition (New or Recurrent) or Death

BENCHMRK 1 & 2: Time to First AIDS-Defining Condition (New or Recurrent) or Death


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12BENCHMRK 1 & 2: Exposure-Adjusted Rates And Relative Risk (95% CI) of Confirmed AIDS-Defining Conditions and Death (Double-Blind and Open-Label)

BENCHMRK 1 & 2: Exposure-Adjusted Rates And Relative Risk (95% CI) of Confirmed AIDS-Defining Conditions and Death (Double-Blind and Open-Label)


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ACTG A5164: Objective -- A Randomized Phase IV Strategy TrialACTG A5164: Objective -- A Randomized Phase IV Strategy Trial

Determine Optimal Timing of Antiretroviral Therapy Initiation With:

• An acute AIDS-related opportunistic infection

• A serious bacterial infection

Compare Two Possible Strategies:

Adapted from Andrew Zolopa. ICAAC/IDSA 2008; abstract 4235.

Early/Immediate Antiretroviral Therapy Intended to be initiated during the treatment of the

acute opportunistic or bacterial infection

Deferred Antiretroviral Therapy Intended to be initiated after treatment for acute opportunistic or bacterial infection is completed

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ACTG A5164: Baseline Clinical CharacteristicsACTG A5164: Baseline Clinical Characteristics

Characteristic Immediate Deferred Total

HIV RNA (log10) Median (IQR) 5.07 (4.74 – 5.59) 5.08 (4.64 – 5.64) 5.07 (4.71 – 5.63 )

CD4+ (cells/mm3) Median (IQR) 31 (12 – 54) 28 (10 – 56) 29 (10 – 55)

Multiple OI/BI Within 30 Days 32% 33% 33%

BI n (%) 17 (12) 17 (12) 34 (12)

PCP n (%) 88 (62) 89 (63) 177 (63)

Other OI n (%) 36 (26) 35 (25) 71 (25)

CMV n (%) 4 (3) 2 (1) 6 (2)

Crypto/Histo n (%) 20 (14) 25 (18) 45 (16)

MAC n (%) 3 (2) 3 (2) 6 (2)

Toxoplasmosis n (%) 9 (6) 4 (3) 13 (5)

No Prior ART n (%) 131 (93) 128 (91) 259 (92)

OI = opportunistic infection; BI = bacterial infection; PCP = pneumocystis pneumonia ; CMV = cytomegalovirus; MAC = mycobacterium avium complex P values = ns


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ACTG A5164: Time to AIDS Progression or DeathACTG A5164: Time to AIDS Progression or Death

00.10.20.30.40.50.60.70.80.9

1

4 12 20 28 36 44

Immediate

Deferred

Pro

bab

ilit

y o

f S

urv

ivin

g W

ith

ou

t D

eath

/New

AID

S-D

efin

ing

Ill

nes

s

Time to Death/New AIDS-Defining Illness (Weeks)

HR = 0.5395% CI (0.3 to 0.92)

P = 0.02

116

94


48

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Hospitalization Rates by Virologic Response Over Time After HAARTHospitalization Rates by Virologic Response Over Time After HAART

Stephen Berry et al. ICAAC/IDSA 2008; abstract H-2292. Reprinted with permission.

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NA-ACCORD: Distribution of Study PatientsNA-ACCORD: Distribution of Study Patients

First CD4+ Count Between 351 – 500 Measured 1996 – 2006

No Prior AIDS Diagnosis or ARVs (n = 8,374)

Defer HAARTn = 5,901

Initiate HAARTn = 2,473

Transit to CD4+ < 350

Defer HAARTn = 2,229

Initiate HAARTn = 1,220

No Transitn = 2,452

Deaths (Person-Years) in Cohort Analysis

100 (5,815) 137 (5,526) 209 (5,295) 221 (8,358)

Percent Censored in IPW Analysis

57% 0% 10% 0%

Adapted from Mari Kitahata et al. ICAAC/IDSA 2008; abstract H-896b.

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NA-ACCORD: Baseline Characteristics In Study PatientsNA-ACCORD: Baseline Characteristics In Study Patients

Defer HAART n = 5,901

Initiate HAART n = 2,473

Follow Up Person-Years 16,636 8,358

Hepatitis C Virus Infection (%)* 34 27

History of Injection Drug Use (%)* 21 16

Males (%) 75 83

Median Age Years (IQR) 38 (32, 45) 40 (34, 48)

Median CD4+ Count Cells/mm3 (IQR) 432 (391, 468) 421 (386, 459)

Median log10 HIV RNA Copies/mL (IQR)* 4.1 (3.3, 4.6) 4.3 (3.1, 4.9)

White (%) 38 39

*Among patients with known status


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NA-ACCORD: HAART Initiation, Year And RegimenNA-ACCORD: HAART Initiation, Year And Regimen

Defer HAART &Initiate 200 – 350

n = 1,220

Initiate HAART351 – 500n = 2,473

Median (IQR) CD4+ Count Cells/mm3 Prior to HAART Initiation

275 (210, 317)

421 (386, 459)

Median (IQR) Time in Months From First CD4+ Count in the Interval to HAART

2(< 1 – 7)

1(< 1 – 3)

Median Month/Year HAART Initiation (IQR) 5/01 (1/99, 5/03) 1/00 (5/98, 1/02)

Type of Initial HAART Regimen (%)

NNRTI-Based 39 34

PI-Based (Boosted) 12 9

PI-Based (Non-Boosted) 37 46

NNRTI & PI-Based 3 4

> 3 NRTIs 8 7


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20NA-ACCORD: Inverse Probability Weighted Cox Regression Multivariate Analysis

NA-ACCORD: Inverse Probability Weighted Cox Regression Multivariate Analysis

RH* 95% CI P Value

Deferral of HAART at 351 – 500 1.7 1.4, 2.1 < 0.001

Older Age (Per 10 Years) 1.6 1.5, 1.8 < 0.001

Female Sex 1.1 0.9, 1.5 0.290

Baseline CD4 Count (Per 100 Cells/mm3) 0.9 0.7, 1.0 0.083

• Results were similar when restricting the analysis to the 77% of participants with baseline HIV RNA data• Adjusted RH for deferral vs. immediate treatment was also 1.7; 95% C.I. was 1.4, 2.2; and P value was < 0.0001• HIV RNA was not an independent predictor of mortality

RH = relative hazard; CI = confidence interval*Stratified by cohort and year


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When to Start: Indications for Initiation of Antiretroviral TherapyWhen to Start: Indications for Initiation of Antiretroviral Therapy

U.S. Dept of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. 2008 Nov 3. Reprinted with permission.

Section of D.H.H.S. Guidelines for the

Use of Antiretroviral Agents in HIV-1

Infected Adults and Adolescents:

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22Perceptions of HIV-Infected Women: Percentage Who Felt That Culture, Ethnicity Or Language Impacted the Care Received, By Race/Ethnicity

Perceptions of HIV-Infected Women: Percentage Who Felt That Culture, Ethnicity Or Language Impacted the Care Received, By Race/Ethnicity

Adapted from Sally Hodder et al. ICAAC/IDSA 2008; abstract H-443.

^P < 0.05 Caucasian vs. Hispanic and African American

*P < 0.05 Hispanic vs. Caucasian and African American

Total, n = 700Hispanic, n = 147

Caucasian, n = 105African American, n = 448

4129

6239

2132

1021

3838

2740

0 10 20 30 40 50 60 70

Percentage

Not At All

A Little

A Lot

Total Hispanic Caucasian African American

*

*

^

^

^

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23Perceptions of HIV-Infected Women: Percentage Who Felt That Culture, Ethnicity Or Language Impacted the Care Received, By Provider Type

Perceptions of HIV-Infected Women: Percentage Who Felt That Culture, Ethnicity Or Language Impacted the Care Received, By Provider Type

Sally Hodder et al. ICAAC/IDSA 2008; abstract H-443. Reprinted with permission.

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24Use of HAART Among HIV-Infected Women, 2002 – 2005: Characteristics of Study Sample

Use of HAART Among HIV-Infected Women, 2002 – 2005: Characteristics of Study Sample

Adapted from Marsha Lillie-Blanton et al. ICAAC/IDSA 2008; abstract H-444.

2002 2005Number Percent Number Percent

1,463 100% 1,354 100%

Race/Ethnicity1

African American (non-Hispanic) 839 57.4% 778 57.5%Hispanic 432 29.5% 390 28.8%

White (non-Hispanic) 192 13.1% 186 13.7%

Age< 40 502 34.3% 290 21.4%

40 - 49 704 48.1% 677 50.0%50+ 257 17.6% 387 28.6%

CD4+Count

(Cells/ml)

Low (< 200)% 254 17.4% 211 15.6%Medium (200 - 500)% 652 44.6% 603 44.5%

High (> 500)% 516 35.3% 512 37.8%Missing 41 2.8% 28 2.1%

Viral Load

≤ 10,000 1065 72.8% 1056 78.0%> 10,000 373 25.5% 268 19.8%Missing 25 1.7% 30 2.2%Mean 37,124 24,326

Median 450 80Hepatitis C+ 449 30.7% 389 28.7%

Crack,Cocaine,Heroin

Never Used 593 40.5% 561 41.4%Used prior to study only 389 26.6% 320 23.6%

Used earlier during study 323 22.1% 316 23.3%Used in past 6 months 144 9.8% 130 9.6%

Missing 14 1.0% 27 2.0%1Women of “Other” racial/ethnic groups are not included in this analysis.

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Use of HAART Among HIV-Infected Women: Key Findings, Bivariate AnalysisUse of HAART Among HIV-Infected Women: Key Findings, Bivariate Analysis

Marsha Lillie-Blanton et al. ICAAC/IDSA 2008; abstract H-444. Reprinted with permission.

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26Reported AIDS Cases in the United States Among Female Adults and Adolescents, by Region and Race/Ethnicity, 2006

Reported AIDS Cases in the United States Among Female Adults and Adolescents, by Region and Race/Ethnicity, 2006

Aadia I Rana et al. ICAAC/IDSA 2008; abstract H-453. Reprinted with permission.

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27Pregnancies Among HIV-Infected Women in Mississippi: Baseline Demographic Data

Pregnancies Among HIV-Infected Women in Mississippi: Baseline Demographic Data


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Pregnancies Among HIV-Infected Women In Mississippi: Clinical CharacteristicsPregnancies Among HIV-Infected Women In Mississippi: Clinical Characteristics


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29Pregnancies Among HIV-Infected Women In Mississippi: Number of Visits to an HIV Provider Within 12 Months Postpartum

Pregnancies Among HIV-Infected Women In Mississippi: Number of Visits to an HIV Provider Within 12 Months Postpartum


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Compliance With Breast Cancer Screening Guidelines in the HIV ClinicCompliance With Breast Cancer Screening Guidelines in the HIV Clinic

Eleni Patrozou et al. ICAAC/IDSA 2008; abstract H-2339. Reprinted with permission.

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31SUN Study: Factors Associated with Low Bone Mineral Density in a Large Cohort of HIV-Infected U.S. Adults -- Baseline Results

SUN Study: Factors Associated with Low Bone Mineral Density in a Large Cohort of HIV-Infected U.S. Adults -- Baseline Results

Turner Overton et al. CROI 2007; abstract 836. Reprinted with permission.

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32HIV-Infected and -Uninfected Interaction With Testosterone On Bone Mineral Density: T-Scores of Patients in Normal, Osteopenic And Osteoporotic Range

HIV-Infected and -Uninfected Interaction With Testosterone On Bone Mineral Density: T-Scores of Patients in Normal, Osteopenic And Osteoporotic Range

Ranjani Raghunathan et al. ICAAC/IDSA 2008; abstract H-2299. Reprinted with permission.

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33HIV-Infected and -Uninfected Interaction With Testosterone On Bone Mineral Density: T-Scores of Patients With Low and Normal Free Testosterone Levels

HIV-Infected and -Uninfected Interaction With Testosterone On Bone Mineral Density: T-Scores of Patients With Low and Normal Free Testosterone Levels

Ranjani Raghunathan et al. ICAAC/IDSA 2008; abstract H-2299. Reprinted with permission.

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Should Vitamin D Be Prescribed With TDF/FTC? (1)Should Vitamin D Be Prescribed With TDF/FTC? (1)

Kathryn Childs et al. ICAAC/IDSA 2008; abstract H-2300. Reprinted with permission.

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Should Vitamin D Be Prescribed With TDF/FTC? (2)Should Vitamin D Be Prescribed With TDF/FTC? (2)

Kathryn Childs et al. ICAAC/IDSA 2008; abstract H-2300. Reprinted with permission.

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SMART: Study DesignSMART: Study Design

Adapted from Wafaa El-Sadr, M.D., M.P.H., et al. N Engl J Med. 2006;355(22):2283-2296.

CD4+ Cell Count > 350 Cells/mm3

n = 5,472ART Experienced: 95.4%

HIV RNA < 400 Copies/mL: 72%Median CD4+ Count: 597 Cells/mm3

Drug Conservation (DC) StrategyDefer use of ART until CD4+ < 250;

then episodic ART based on CD4+ cell count to increase counts to > 350

n = 2,720

Virologic Suppression (VS) Strategy

Continuous use of ART to maintain viral load as low as possible

n = 2,752

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SMART: Percent Change in Spine Bone Mineral Density, by DXASMART: Percent Change in Spine Bone Mineral Density, by DXA

Adapted from Birgit Grund et al. ICAAC/IDSA 2008; abstract H-2312a.

-4 -3 -2 -1 0 1 2

4

3

2

1

Ye

ars

Change From Baseline (%)

VS Group DC Group

n = 112

n = 88

n = 77

n = 54

n = 47

n = 10

n = 96

n = 15

Est. DC-VS Differences (Mean Change) and P Values

Est. Diff. P

1 Year 1.7 0.003

2 Years 0.8 0.26

3 Years 0.5 0.64

4 Years 2.1 0.40

Through Follow-Up

1.2 0.05

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SMART: Percent Change in Total Hip Bone Mineral Density, by DXASMART: Percent Change in Total Hip Bone Mineral Density, by DXA

Adapted from Birgit Grund et al. ICAAC/IDSA 2008; abstract H-2312a.

-4 -3 -2 -1 0 1 2

4

3

2

1

Ye

ars

Change From Baseline (%)

VS Group DC Group

n = 109

n = 86

n = 75

n = 51

n = 47

n = 9

n = 95

n = 15

Est. DC-VS Differences (Mean Change) and P Values

Est. Diff. P

1 Year 1.3 0.002

2 Years 1.7 0.005

3 Years 1.0 0.27

4 Years 2.5 0.21

Through Follow-Up

1.4 0.002

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• This presentation was created to accompany The Body PRO's summaries of key research presented at ICAAC/IDSA 2008, by Benjamin Young, M.D., Ph.D.

• The Body PRO's extensive coverage of ICAAC/IDSA 2008 also includes:– Summaries and analyses of research on a wide array of clinical

subjects.– Interviews with top researchers discussing the results of noteworthy

studies.– Audio podcasts you can play online or download to your computer or

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• Visit TheBodyPRO.com/ICAAC2008 today for a full listing of our conference coverage!

Disclaimer:The Body PRO is designed for educational purposes only and is not engaged in rendering medical advice or professional services. The information provided through The Body PRO should not be used for diagnosing or treating a health problem or a disease.

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THE BODY PRO The HIV Resource for Health Professionals Faculty: Benjamin Young, M.D., Ph.D. Assistant Clinical Professor of Medicine at the University