THE BODY PRO The HIV Resource for Health

THE BODY PRO The HIV Resource for Health

THE BODY PRO The HIV Resource for Health Professionals Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 Faculty: Benjamin Young, M.D., Ph.D. Assistant Clinical Professor of Medicine at the University of Colorado Benjamin Young, M.D., Ph.D. The Body PRO Covers ICAAC/IDSA 2008 Washington, D.C.; October 25-28, 2008 This activity is jointly sponsored by Postgraduate Institute for Medicine and The Body PRO. Copyright 2008 The HealthCentral Network, Inc. All rights reserved. 2 Faculty for This Activity The Body PRO 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. Disclosures Dr. 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 Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 The Body PRO HOPS: Incidence of High Frequency Infectious Opportunistic Infections, 1994 2006 JT Brooks et al. ICAAC/IDSA 2008; abstract H-2330. Reprinted with permission. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 3 4 The Body PRO HOPS: Incidence Rates of Malignant Opportunistic Infections, 1994 2006

JT Brooks et al. ICAAC/IDSA 2008; abstract H-2330. Reprinted with permission. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 The Body PRO HOPS: Median CD4+ Cell Counts at Opportunistic Infection Diagnosis, 1994 2006 JT Brooks et al. ICAAC/IDSA 2008; abstract H-2330. Reprinted with permission. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 5 6 The Body PRO DUET: Study Design and Major Inclusion Criteria Richard Haubrich et al. ICAAC/IDSA 2008; abstract H-1239. Reprinted with permission. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 7 The Body PRO DUET: Proportion of Patients With

Any ADE or Death Richard Haubrich et al. ICAAC/IDSA 2008; abstract H-1239. Reprinted with permission. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 8 The Body PRO DUET: Proportion of Patients Hospitalized by Week 48* Richard Haubrich et al. ICAAC/IDSA 2008; abstract H-1239. Reprinted with permission. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 9 The Body PRO DUET: Cumulative Hospital Days Over 48 Weeks Richard Haubrich et al. ICAAC/IDSA 2008; abstract H-1239. Reprinted with permission. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 10 BENCHMRK 1 & 2: Study Design The Body PRO

Randomized, double-blind, placebo-controlled with Data and Safety Monitoring Board Primary analysis at Week 16; secondary analysis at Week 48 Primary Endpoints Week 16 HIV-1-infected Triple-class resistant HIV-1 RNA > 1,000 copies/mL No CD4 cell cut-off Protocol 018* (n = 352) Europe, Asia/Pacific and Peru Protocol 019* (n = 351) North and South America Planned Duration Week 240 Raltegravir 400 mg BID + OBT P018* (n = 234) P019* (n = 232) 2:1 Placebo + OBT P018* (n = 118) P019* (n = 119) 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 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. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008

The Body PRO BENCHMRK 1 & 2: Time to First AIDS-Defining Condition (New or Recurrent) or Death 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. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 11 The Body PRO BENCHMRK 1 & 2: Exposure-Adjusted Rates And Relative Risk (95% CI) of Confirmed AIDS-Defining Conditions and Death (Double-Blind and Open-Label) 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. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 12 13 The Body PRO

ACTG 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: 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 Adapted from Andrew Zolopa. ICAAC/IDSA 2008; abstract 4235. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 14 The Body PRO ACTG 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) 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) n (%) 131 (93) 128 (91) 259 (92) Multiple OI/BI No Prior ART OI = opportunistic infection; BI = bacterial infection; PCP = pneumocystis pneumonia ; CMV = cytomegalovirus; MAC = mycobacterium avium complex P values = ns Adapted from Andrew Zolopa. ICAAC/IDSA 2008; abstract 4235. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 15 Probability of Surviving Without Death/New AIDS-Defining Illness The Body PRO ACTG A5164: Time to AIDS Progression or Death 1 0.9 0.8

0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 116 94 Immediate Deferred HR = 0.53 95% CI (0.3 to 0.92) P = 0.02 4 12 20 28 36 44 48 Time to Death/New AIDS-Defining Illness

(Weeks) Adapted from Andrew Zolopa. ICAAC/IDSA 2008; abstract 4235. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 16 The Body PRO Hospitalization Rates by Virologic Response Over Time After HAART Stephen Berry et al. ICAAC/IDSA 2008; abstract H-2292. Reprinted with permission. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 17 The Body PRO NA-ACCORD: Distribution of Study Patients First CD4+ Count Between 351 500 Measured 1996 2006 No Prior AIDS Diagnosis or ARVs (n = 8,374) Defer HAART n = 5,901 Initiate HAART n = 2,473 Transit to CD4+ < 350

Defer HAART n = 2,229 Initiate HAART n = 1,220 No Transit n = 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. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 18

NA-ACCORD: Baseline Characteristics In Study Patients The Body PRO Defer HAART n = 5,901 Initiate HAART n = 2,473 16,636 8,358 Hepatitis C Virus Infection (%)* 34 27 History of Injection Drug Use (%)* 21 16 Males (%) 75 83

38 (32, 45) 40 (34, 48) 432 (391, 468) 421 (386, 459) 4.1 (3.3, 4.6) 4.3 (3.1, 4.9) 38 39 Follow Up Person-Years Median Age Years (IQR) Median CD4+ Count Cells/mm3 (IQR) Median log10 HIV RNA Copies/mL (IQR)* White (%) *Among patients with known status Adapted from Mari Kitahata et al. ICAAC/IDSA 2008; abstract H-896b. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 19 The Body PRO

NA-ACCORD: HAART Initiation, Year And Regimen Defer HAART & Initiate 200 350 n = 1,220 Initiate HAART 351 500 n = 2,473 275 (210, 317) 421 (386, 459) 2 (< 1 7) 1 (< 1 3) 5/01 (1/99, 5/03) 1/00 (5/98, 1/02) NNRTI-Based 39 34 PI-Based (Boosted) 12 9 PI-Based (Non-Boosted) 37 46 NNRTI & PI-Based 3 4 > 3 NRTIs 8 7 Median (IQR) CD4+ Count Cells/mm3 Prior to HAART Initiation Median (IQR) Time in Months From First CD4+ Count in the Interval to HAART Median Month/Year HAART Initiation (IQR) Type of Initial HAART Regimen (%)

Adapted from Mari Kitahata et al. ICAAC/IDSA 2008; abstract H-896b. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 The Body PRO 20 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 RH = relative hazard; CI = confidence interval *Stratified by cohort and year 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 Adapted from Mari Kitahata et al. ICAAC/IDSA 2008; abstract H-896b. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 21 The Body PRO When to Start: Indications for Initiation of Antiretroviral Therapy Section of D.H.H.S. Guidelines for the Use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents: 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. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 Perceptions of HIV-Infected Women: Percentage Who Felt That Culture, Ethnicity Or Language Impacted the Care Received, By Race/Ethnicity The Body PRO 40 27 ^ A Lot 38 38

^P < 0.05 Caucasian vs. Hispanic and African American 21 10 ^ A Little 32 * 21 *P < 0.05 Hispanic vs. Caucasian and African American 39 Not At All 62 ^ 29 * 0 10 20 41 30

40 50 60 70 Percentage Total Hispanic Caucasian African American Total, n = 700 Hispanic, n = 147 Caucasian, n = 105 African American, n = 448 Adapted from Sally Hodder et al. ICAAC/IDSA 2008; abstract H-443. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 22 The Body PRO 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. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 23 24 Use of HAART Among HIV-Infected Women, 2002 2005: Characteristics of Study Sample The Body PRO 2002 Race/ Ethnicity1 Age CD4+ Count (Cells/ml) Viral Load African American (non-Hispanic) Hispanic White (non-Hispanic) < 40 40 - 49 50+ Low (< 200)% Medium (200 - 500)% High (> 500)% Missing 10,000 > 10,000 Missing Mean Median Hepatitis C+ Crack, Cocaine, Heroin 1 Never Used Used prior to study only Used earlier during study Used in past 6 months Missing Number 1,463 839 432 192 502 704 257

254 652 516 41 1065 373 25 2005 Percent 100% 57.4% 29.5% 13.1% 34.3% 48.1% 17.6% 17.4% 44.6% 35.3% 2.8% 72.8% 25.5% 1.7% 37,124 450 449 593 389 323 144

14 30.7% 40.5% 26.6% 22.1% 9.8% 1.0% Number Percent 1,354 100% 778 57.5% 390 28.8% 186 13.7% 290 21.4% 677 50.0% 387 28.6% 211 15.6% 603 44.5% 512 37.8% 28

2.1% 1056 78.0% 268 19.8% 30 2.2% 24,326 80 389 28.7% 561 41.4% 320 23.6% 316 23.3% 130 9.6% 27 2.0% Women of Other racial/ethnic groups are not included in this analysis. Adapted from Marsha Lillie-Blanton et al. ICAAC/IDSA 2008; abstract H-444. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 25 Use of HAART Among HIV-Infected Women: Key Findings, Bivariate Analysis The Body PRO

Marsha Lillie-Blanton et al. ICAAC/IDSA 2008; abstract H-444. Reprinted with permission. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 The Body PRO 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. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 26 The Body PRO Pregnancies Among HIV-Infected Women in Mississippi: Baseline Demographic Data Aadia I Rana et al. ICAAC/IDSA 2008; abstract H-453. Reprinted with permission. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 27 28 Pregnancies Among HIV-Infected Women

In Mississippi: Clinical Characteristics The Body PRO Aadia I Rana et al. ICAAC/IDSA 2008; abstract H-453. Reprinted with permission. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 The Body PRO Pregnancies Among HIV-Infected Women In Mississippi: Number of Visits to an HIV Provider Within 12 Months Postpartum Aadia I Rana et al. ICAAC/IDSA 2008; abstract H-453. Reprinted with permission. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 29 30 The Body PRO Compliance With Breast Cancer Screening Guidelines in the HIV Clinic Eleni Patrozou et al. ICAAC/IDSA 2008; abstract H-2339. Reprinted with permission. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 The Body PRO

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. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 31 The Body PRO 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. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 32 The Body PRO 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.

Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 33 34 The Body PRO Should Vitamin D Be Prescribed With TDF/FTC? (1) Kathryn Childs et al. ICAAC/IDSA 2008; abstract H-2300. Reprinted with permission. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 35 The Body PRO Should Vitamin D Be Prescribed With TDF/FTC? (2) Kathryn Childs et al. ICAAC/IDSA 2008; abstract H-2300. Reprinted with permission. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 36 SMART: Study Design The Body PRO CD4+ Cell Count > 350 Cells/mm3

n = 5,472 ART Experienced: 95.4% HIV RNA < 400 Copies/mL: 72% Median CD4+ Count: 597 Cells/mm3 Drug Conservation (DC) Strategy Defer 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 Adapted from Wafaa El-Sadr, M.D., M.P.H., et al. N Engl J Med. 2006;355(22):2283-2296. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 37 The Body PRO SMART: Percent Change in Spine Bone Mineral Density, by DXA VS Group DC Group n = 112

1 n = 96 Est. DC-VS Differences (Mean Change) and P Values n = 88 2 Est. Diff. Years n = 77 3 1 Year 1.7 0.003 2 Years 0.8 0.26 n = 54 3 Years

0.5 0.64 n = 47 4 Years 2.1 0.40 Through Follow-Up 1.2 0.05 n = 10 4 P n = 15 -4 -3 -2

-1 0 1 2 Change From Baseline (%) Adapted from Birgit Grund et al. ICAAC/IDSA 2008; abstract H-2312a. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 38 The Body PRO SMART: Percent Change in Total Hip Bone Mineral Density, by DXA VS Group 1 DC Group n = 109 n = 95 Est. DC-VS Differences (Mean Change) and P Values Years

2 3 4 n = 86 Est. Diff. n = 75 P 1 Year 1.3 0.002 2 Years 1.7 0.005 n = 51 3 Years 1.0

0.27 n = 47 4 Years 2.5 0.21 Through Follow-Up 1.4 0.002 n=9 n = 15 -4 -3 -2 -1 0 1

2 Change From Baseline (%) Adapted from Birgit Grund et al. ICAAC/IDSA 2008; abstract H-2312a. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008 39 The Body PRO 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 MP3 player. Narrated, online slide presentations highlighting major study results. 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. Reappraising Key Issues in HIV Clinical Management: Highlights From ICAAC/IDSA 2008

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