complications of hiv/haart: a summary of key croi 2008 research complications of hiv/haart the body...

Complications of HIV/HAART: A Summary of Key CROI 2008 Research

Complications ofHIV/HAART

The Body PRO Coverage of the 15th Conference on Retroviruses and Opportunistic Infections (CROI 2008)

February 3-6, 2008Boston, Mass.

Faculty:Kathryn Anastos, M.D.Cal Cohen, M.D., M.S.David Wohl, M.D.

David Wohl, M.D.

CROI 2008:Coverage From

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Kathryn Anastos, M.D.Kathryn Anastos, M.D., is the Executive Co-Director for Clinical and Scientific Programs of WE-ACTx (Women's Equity in Access to Care and Treatment, a community-based organization committed to providing HIV primary care, including antiretroviral therapy, to female survivors of genocidal rape in Rwanda. She has also developed and serves as the Principal Investigator of the Rwandan Women's Cohort Study (RWISA), funded by the U.S. National Institutes of Health (NIH). She is currently Professor of Medicine, Epidemiology and Population Health at Albert Einstein College of Medicine, Bronx, N.Y. Additionally, since 1993, Dr. Anastos has served as the Principal Investigator for the New York City/Bronx Consortium of the Women's Interagency HIV Study (WIHS), also funded by NIH.

Cal Cohen, M.D., M.S.Dr. Cal Cohen is the research director of Harvard Vanguard Medical Associates and Community Research Initiative of New England in Boston, Mass. He is also a clinical instructor at Harvard Medical School. In addition, he works as an HIV clinical management consultant and internist at Harvard Pilgrim Health Care. Dr. Cohen holds appointments at Brigham and Women's Hospital and Beth Israel Hospital, both in Boston, Mass. In addition to caring for HIV-infected patients and directing clinical research at a large HIV community-based research site, Dr. Cohen is actively involved in evaluating new antiretroviral therapies, the durability and longevity of the benefits from such therapies and issues regarding compliance and adherence. Dr. Cohen has served as a consultant to or has received honoraria or research support from Abbott Laboratories, Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline and Tibotec.

David Wohl, M.D. Dr. Wohl is an associate professor of medicine at the University of North Carolina at Chapel Hill, and co-directs HIV services for the North Carolina Department of Corrections. Dr. Wohl is an investigator in the NIAID-sponsored AIDS Clinical Trials Group (ACTG) and a member of the ACTG Complications of HIV Disease Research Agenda Committee. His research focuses on metabolic and infectious complications of HIV and its therapies, as well as issues related to medication adherence and access to care—particularly among incarcerated inmates with HIV infection. Dr. Wohl has served as a consultant to or has received honoraria or research support from Abbott Laboratories, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Merck & Co, Roche Laboratories and Tibotec.

This activity is supported by an educational grant from

Faculty


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About This Slide Presentation

• This presentation was created to accompany The Body PRO's summary of key research presented at CROI 2008, featuring reports by Kathryn Anastos, M.D., Cal Cohen, M.D., M.S., and David Wohl, M.D. For more information about this program, please visit us on the Web at: TheBodyPRO.com/CROI2008

• Please feel free to use this slide presentation for personal reference or for your own presentations; however, we ask that you not modify any aspects of the slides contained within this presentation, so proper attribution can be retained. If you would like to publish all or part of this presentation, or repost any of these slides online, permission must first be obtained from Body Health Resources Corporation.

• Our gratitude goes out to all the researchers who granted permission for their slides to be adapted for this presentation.


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Low-Dose Growth Hormone in Patients With Lipodystrophy


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Comparison of Effects on Growth Hormone-Releasing Hormone (GHRH), High Dose Growth Hormone (GH) and Low Dose GH

-25

-20

-15

-10

-5

0GHRH High-Dose

GHLow-Dose

GH

% C

ha

ng

e V

AT

Adapted from Janet Lo et al. CROI 2008; abstract 146LB.


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Effects of Growth Hormone on Glucose Tolerance

100

110

120

130

140

150

160

170

Baseline Month 6 Month 12 Month 18

PlaceboGrowth Hormone

2-H

our

Glu

cose

(m

g/dL

)

Note: No effects on fasting glucose,

insulin or hemoglobin A1c were observed.

Adapted from Janet Lo et al. CROI 2008; abstract 146LB.


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When Does Fat Loss Become Clinically Evident?


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Patients With > 20%, > 30% and > 35% Limb Fat Loss According to the Presence or Absence of Clinically Evident Lipoatrophy (LA)

0.00%

10.00%

20.00%

30.00%

40.00%

50.00%

60.00%

70.00%

80.00%

90.00%

> 20% LimbFat Loss

> 30 % LimbFat Loss

> 35% LimbFat Loss

Clinically Evident LAat 96 Weeks

No Clinically EvidentLA at 96 Weeks

84.6%(11/13)

P = 0.003*36.6%(15/41)

84.6%(11/13)

69.2%(10/13)

P < 0.001*26.8%(11/41)

P = 0.003*24.4%(10/41)

* Statistically significant difference in percentage of patients with limb fat loss between LA no and LA yes groups (Chi-square test)

Daniel Podzamczer et al. CROI 2008; abstract 941. Reprinted with permission.


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Chromium Supplementation and Fat Loss


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Body Composition

Ellie Aghdassi et al. CROI 2008; abstract 936. Reprinted with permission.

Body Fat Mass (%)

10

12

14

16

18

20

22

24

Chromium Placebo

%

Trunk Fat Mass (%)

10

15

20

25

30

Chromium Placebo

Lean Body Mass (%)

70

71

72

73

74

75

76

77

78

79

80

Chromium Placebo

%

Baseline

Wk 16

P = 0.004

P = 0.013

P = 0.003


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Blood Biochemistry

Blood Insulin

0

20

40

60

80

100

120

140

160

180

Chromium Placebo

Pm

ol/L

Insulin Resistance

0

2

4

6

8

10

Chromium Placebo

HO

MA

P = 0.009

P = 0.025

Ellie Aghdassi et al. CROI 2008; abstract 936. Reprinted with permission.

Baseline

Week 16


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HIV and Cardiovascular Problems


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Rates of MI by Use of Various NRTIs

CA Sabin et al. CROI 2008; abstract 957c. Reprinted with permission.


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Cardiovascular Risk Profile atTime of MI



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Association With Recent1 Didanosine and Abacavir Use and Risk of MI: Additional Adjustment for Factors That May Be Influenced By cART

1Recent = still using or stopped within last 6 months*All data depicted are also adjusted for demographic factors, calendar year, cohort, CV risk factors that are unlikely to be modified strongly by cART use and cumulative exposure to other antiretroviral drugs. Hence, the model “No further adjustment” is similar to the results shown in Table 2, model 2



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Rates of MI for Recent1 Use of Didanosine and of Abacavir by Predicted 10-Year Coronary Heart Disease (CHD) Risk

0

5

10

15

20

25

30

35

Overa

llLow

Mod

erat

eHig

h

Unknow

n

No RecentDidanosine

RecentDidanosine

0

5

10

15

20

25

30

35

Ove

rall

Low

Mode

rate

High

Unknown

No RecentAbacavir

RecentAbacavir

Events 393 124 78 24 86 26 134 34 95 40

PY 130184 27728 59281 13102 14289 3383 6914 1474 49700 9770

Stratified by Recent1 Didanosine Use Stratified by Recent1 Abacavir Use

Events 325 192 60 42 79 33 100 68 86 49

PY 126581 31331 57628 14754 13372 4300 6293 2095 49288 10182

Test of interaction between moderate/high CHD risk and recent didanosine use: P = 0.36

Test of interaction between moderate/high CHD risk and recent abacavir use: P = 0.04

1 Recent = still using or stopped within last 6 months



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HIV and Inflammation in STACCATO


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Baseline Biomarkers and All Cause Mortality

Adapted from Lewis Kuller et al. CROI 2008; abstract 139.

*OR is per average difference between 4th and 1st quartile.

Biomarker Adjusted OR* P-Value Un-adjusted OR* P-Value

Amyloid A (mg/L) 2.6 0.09 2.2 0.07

Amyloid P (µg/L) 1.1 0.84 0.7 0.39

D-dimer (µg/mL) 26.5 < 0.0001 12.4 < 0.0001

F1.2 (pmol/L) 1.2 0.66 1.0 0.92

hsCRP (µg/mL) 2.8 0.03 2.0 0.05

IL-6 (pg/mL) 11.8 < 0.0001 8.3 < 0.0001


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Change in D-Dimer‡ (µg/mL) From Baseline to Month 1


0

0.04

0.11

0.28

0 0.1 0.2 0.3 0.4

< 4

00

40

1 t

o1

0,0

00

10

,00

0to

50

,00

0>

50

,00

0

Change in D-Dimer (µg/mL)

Mo

nth

1 H

IV R

NA

Lev

el

(Co

pie

s/m

L)

P = 0.0005 for trend

‡DC patients on ART at baseline with HIV RNA ≤ 400 copies/mL


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Change in Biomarkers From Baseline To Month 1 by Treatment Group


VS Group DC Group

P-Value* nMed M1-bl

(IQR)n

Med M1-bl(IQR)

D-dimer < 0.0001 2480.00

(-0.13 to 0.08)248

0.05(-0.07 to 0.18)

IL-6 < 0.0001 2490.12

(-0.88 to 0.97)247 0.60

(-0.17 to 1.87)

*Wilcoxon 2-sided test comparing DC and VS from baseline to month 1


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Risk of Death Associated With Change in Biomarker Levels From Baseline to Latest Level: Continuous Change on Log10 Scale*

Biomarker P-Value Adjusted OR* 95% CI

Amyloid A (mg/L) 0.09 2.2 0.9 – 5.4

Amyloid P (µg/L) 0.04 0.32 0.11 – 0.94

D-dimer (µg/mL) 0.02 5.0 1.3 – 18.9

F1.2 (pmol/L) 0.77 1.2 0.4 – 3.5

hsCRP (µg/mL) 0.003 5.5 1.8 – 16.5

IL-6 (pg/mL) 0.006 5.3 1.6 – 17.1

*OR is per average difference between 4th and 1st quartile.



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Pro-Inflammatory Markers and Endothelial Dysfunction: s-VCAM-1 and MCP-1 [CCL2]

1600

1750

1900

2050

2200

2350

2500

PT AR 12WK RT

0

15

30

45

60

75

90

PT AR 12WK RT

s-VCAM-1 MCP-1

ng

/mL

pg

/mL

Some effect of retreatment at final visit but not significant

Adapted from Alexandra Calmy. CROI 2008; abstract 140.

PT = Pre-TreatmentAR = At Randomization

P < 0.01 P < 0.05

12WK = At 12 WeeksRT = Re-Treatment

n = 64


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Aging and HIV


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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)

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

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

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

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

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

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

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

P values = ns

Adapted from Andrew Zolopa. CROI 2008; abstract 142.


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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=0.5399%CI (0.25, 1.09)

P = 0.023

116

94


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A5164: Safety Outcomes Over 48 Weeks

Outcome P-Value Immediate Deferred

IRIS Reported 10 13

IRIS Confirmed 8 (5.7%) 12 (8.5%)


Hospitalizations (After Day 30)

Subjects 0.63 39% 36%

Hospital Days (Median) 0.79 5 6


Lab Adverse Events

Grades 2-3-40.77 31 – 39 – 20 36 – 45 – 21

Clinical Adverse Events

Grades 2-3-40.87 14 – 40 – 7 34 – 29 – 6



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Factors Associated With Viral Suppression < 50 Copies/mL Among Homeless and Marginally Housed HIV-Infected Participants in San Francisco* (n = 104)

*The multivariate regression model was

derived including all

variables with a P value < = 0.2.

Sheri D. Weiser et al. CROI 2008; abstract 807. Reprinted with permission.

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