SY26 The Role of Case Management in Optimzing HIV Treatment

The Role of Case Management in Optimizing HIV Treatment

Brady Allen, MD
Trevor Hawkins, MD

SY26
Friday, June 20, 2008 — 7:30 AM‐9:15 AM Gilead

SYMP‐BREAKFAST

ABSTRACT

The availability of potent and easier‐to‐use highly active antiretroviral therapy (HAART)
regimens have led to dramatic improvements in life expectancy and quality of life for most HIV‐
infected patients. Recent guidelines from the Department of Health and Human Services provide essential recommendations
for when to start HAART, what to start with, and what not to use. Studies show that adherence rates of 90% to 95% may be
required to achieve HIV viral suppression, prevention of drug resistance, and improved survival. To this end, successful
antiretroviral therapy requires a lifelong commitment to therapy by both patient and the health care team, and the case
manager plays an integral role as a gate opener to health care and supportive services, health insurance, entitlements, and
helping patients stay on therapy.

This symposium will focus on the role of the case manager in HIV care as it relates to the need to increase the proportion of
persons who are aware of their HIV‐infection status, evidence supporting the earlier initiation of HAART and the use of
continuous therapy, and how to assess and monitor treatment adherence.

OBJECTIVES
1. Describe the health benefits of routine HIV screening.

2. List key adherence and medical considerations when selecting treatment options.

3. Discuss approaches to improving adherence to antiretroviral therapy.

PRESENTER PROFILES
Allen, Brady L., MD has been a general internist treating HIV infection for 25 years. He currently follows over 600 patients.
He has attended every major AIDS conference since 1988.

Disclaimer: Dr. Bray has received honoraria from Abbott and Gilead.

Hawkins, Trevor, MD received his MD from Manchester University in the UK in 1971 and did postgraduate work at Charing
Cross Hospital in London. He left for India in 1975, where for 6 years he was the Medical Director of a small 50 bed hospital.
He saw his first patient with HIV disease in 1986 and thus started his lifelong interest in HIV disease. He is the founder and
Medical Director of the Southwest CARE Center an HIV specialty clinic serving Santa Fe and Northern New Mexico. He is an
associate clinical professor at UNM where he teaches students and residents about HIV and is heavily involved in clinical
research into HIV disease.

Disclaimer: Dr. Hawkins has received honoraria from GS; GSK and Tibotec. He has also served on the speaker’s bureau. Dr.
Hawkins also has an undisclosed relationship with Pfizer, Merck, Abbott, and Monogram.
Opinions expressed in conference sessions and handout materials are those of the speaker and do not reflect the opinion of CMSA, its officers or staff, or the CMSA Annual Conference.
The Role of Case Management
in Optimizing HIV Treatment
Supported by an independent educational

grant from Gilead Sciences Medical Affairs
Update this slide
Welcome
Moderator (TBD)
Faculty
Brady L. Allen, MD
Clinical Attending Physician
Baylor University Medical Center
Dallas, Texas
Trevor N. Hawkins, MD
Associate Clinical Professor
Department of Family Practice
University of New Mexico
Albuquerque, New Mexico
Medical Director and Principal Physician
Southwest CARE Center
Santa Fe, New Mexico
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Update this slide
Agenda
7:30 AM – 7:35 AM Welcome and Introductions
TBD (CMSA Moderator)
7:35 AM – 7:50 AM Health Benefits of Routine HIV Screening

Brady L. Allen, MD
7:50 AM – 8:10 AM Selecting HAART: Adherence and Medical

Considerations
Brady L. Allen, MD
8:10 AM – 8:45 AM Approaches to Improving Adherence

Trevor N. Hawkins, MD
9:00 AM – 9:15 AM Question and Answer Session
Contact Hours Statement

This activity has been submitted for approval to the following accrediting bodies for
1.5 (60 min) contact hours: Commission for Case Manager Certification (CCMC),
Commission on Rehabilitation Counselor Certification (CRCC), Commission for
Certified Disability Management Specialists (CDMS), and 1.50 (60 min) contact hours:
National Association of Social Workers.
CMSA is approved provider of nursing education by the California Board of Registered

Nursing, Provider CEP11460. California Board of Registered Nursing contact hours
are based on a 50-
50-minute hour. An application has been submitted to the
Arkansas Nurses Association, an accredited provider of continuing education in
nursing by the American Nurses Credentialing Center's Commission on Accreditation
(ANCC--COA). Please call Kesha James at Case Management Society of American for
(ANCC
more information about contact hours. Application for Continuing Medical Education
(CME) credit has been filed with American Board of Quality Assurance and Utilization
Review Physicians, Inc. Determination of credits is pending. Registrants may also
access COHN, COHN-
COHN-S/CM, and CRRN hours.
Attendees will be awarded contact hour credit upon verification of attendance and
online submission of a completed program evaluation onsite or up to 30 days post
conference. Certificates will be issued online prior to attendees' completion of
program evaluation.
Vested Interest/Disclosures
Brady L. Allen, MD Trevor N. Hawkins, MD
Grants/Research None None

Support
Consultant None None
Speaker’s Bureau Abbott Laboratories, Abbott Laboratories, Gilead

Gilead Sciences Sciences, GlaxoSmithKline,
Merck, Monogram, Pfizer,
Tibotec
Honoraria Abbott Laboratories, Abbott Laboratories, Gilead

Gilead Sciences Sciences, GlaxoSmithKline,
Merck, Monogram, Pfizer,
Tibotec
Stock Holder None None

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Program Evaluation
Your feedback is essential for measuring
the success of this CE program.
Attendees are able to evaluate session content and

print CE certificates onsite.
Designated CE stations will be available at the expanded Cyber

Café throughout the conference. You may also access your
personal CE account from any computer with internet access.
Attendees have up to 30-days post conference to evaluate

sessions and print CE certificates.
Learning Objectives
● Describe the health benefits of routine HIV
screening
● List key adherence and medical considerations
when selecting treatment options
● Discuss approaches to improving adherence to
antiretroviral therapy
Health Benefits of
Routine HIV Screening
Brady L. Allen, MD
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Estimated Number of AIDS Cases and Deaths
Among US Adults and Adolescents (1985-2005)
90 450
AIDS
80 400
Prevalence
Number of AIDS Cases and
70 350
AIDS
Prevalence (x1000)
Deaths (x1000)
60 Cases 300
50 250
40 200
30 150
20 100
AIDS
10 Deaths 50
0 0
85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05
Year of Diagnosis or Death
CDC. HIV/AIDS Surveillance Report. June 2007;17. Revised Edition.

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Awareness of HIV Serostatus:

Estimates of Transmission
100
~25%
90 Unaware
of Infection
80 ~54%
of New
70 Infections
60
Percent
50
~75%
40 Aware
of Infection
30 ~46%
of New
20 Infections
10
0
People Living With HIV New Sexual infections/Year
(1,039,000-1,185,000) (~32,000)
Marks G. AIDS. 2006;20:1447-1450.

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Reduction in Risk Behaviors

Once Seropositive Status Is Known
Reduction in Prevalence of Unprotected Intercourse
Relative to HIV-Positive Persons Unaware of Serostatus
0
Reduction in Prevalence (%)
-20
-40
-53%
-60
-68%
-80
HIV-Positive Persons Aware HIV-Positive Persons Aware
of Their Own Serostatus of Their Own Serostatus
and HIV-Negative Partner
Marks G, et al. JAIDS. 2005;39:446-453.

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Missed Opportunities:
South Carolina Experience (1997-2005)
● Retrospective review of 4315 persons with HIV
infection in South Carolina
- 41.3% developed AIDS within 1 year of HIV diagnosis
(late testers)
● Among late testers
- 73% made a total of 7988 health-care visits prior to
HIV diagnosis
Duffus W, et al. MMWR. 2006;55(47):1269-1272.

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“Late Testers” Account for

Approximately 40% of HIV Diagnoses
Males Females
80 Early tester 80 Early tester
Late tester Late tester
70 70
63% 65%
60 59% 60%
60
HIV Diagnosis (%)
HIV Diagnosis (%)
53% 53% 54%

50%
50 47% 47% 50 46%
41% 40%
40 37% 40
35%
30 30
20 20
10 10
0 0
MSM IDU MSM Hetero- Other IDU Hetero- Other
+ IDU sexual sexual
CDC. HIV/AIDS Surveillance Report. June 2007;17. Revised Edition.

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National HIV Behavioral Surveillance:

Unrecognized HIV Infection
● Cross-sectional study Unrecognized Infection
- 5-city data collection
100
system
- Men who have sex with 80 79%
men 70%
Prevalence (%)
- 83% participation rate 60

49%
● Participants tested for 40 34%
HIV infection 30%
- Surveyed about knowledge 20

of their HIV status
0
18-24 25-29 30-39 40-49 >50
Age Group (years)
Branson BM, et al. MMWR Recomm Rep. 2006;55(RR-14):1-17.

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Evidence for Revising
Recommendations
● Many HIV-infected persons access health care but are
not tested for HIV until symptomatic
● Routine HIV screening is cost effective, and effective
treatment is available
● Opt-out screening increases testing rates
● Awareness of HIV infection leads to substantial
reductions in high-risk sexual behavior
● Inconclusive evidence about prevention benefits from
typical counseling for persons who test negative
● Great deal of experience with HIV testing, including rapid
tests
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Revised CDC Recommendations for

HIV Testing in Healthcare Settings
● Routine voluntary testing for
patients ages 13 to 64 years in
healthcare settings
- Not based on patient risk
● Opt-out testing
● No separate consent for HIV
● Pretest counseling not
required
● Repeat HIV testing left to
discretion of provider
- Based on patient risk

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Opt-Out Versus Opt-In Screening

Opt-Out Screening Opt-In Screening
● Implies all patients are ● Requires providers to
considered candidates for specifically recommend HIV
screening testing and for patients to
● Testing is part of standard specifically agree to testing
panel of tests ● May assume that clinicians
● Patients can decline test, but assess which patient is at-risk
test is performed unless for infection
patient specifically refuses ● Greater reluctance on part of
patient
● Requires more staff time

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Adults and Adolescents:
Recommendations for HIV-Screening Location
● All primary care settings
● Emergency departments, in-patient services, and urgent
care clinics
● Public health settings
- Tuberculosis clinics
- Sexually transmitted diseases clinics
- Substance abuse treatment centers
- Correctional facility treatment centers
● Screening may be discontinued in low-prevalence
communities with demonstrated yield <1:1000

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Cost-Effectiveness of Screening the

General Population for HIV
HIV Prevalence
70000 1.0%
Dollars per Quality-Adjusted
$60,700 0.1%
60000 $55,500 Not Cost
Life-Year Gained
Effective
50000
Cost
40000 Effective
$30,800 $32,300
30000
20000
10000
0
Screening Screening Screening
Once Every 5 Years Every 3 Years
Paltiel AD, et al. Ann Intern Med. 2006;145:797-806.

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Availability of Rapid HIV Testing

in Academic EDs
● Cross-sectional National survey of academic EDs (n=128)
- 102 (80%) responded (12/06 to 3/07)
● Results
- 57% offered rapid HIV testing
• 45% allowed providers to order tests without restrictions
- Only 59% could link an HIV-positive patient to subspecialty care
• 55% had policies/guidelines on its use
- All did allow testing following occupational exposure
- Key factors that may influence adoption of rapid HIV testing in EDs
• Timely presence of HIV counselor
• Ability to link patients to HIV speciality care providers
• Presence of point person among ED faculty
• Quick return of rapid HIV test results
Ehrenkranz PD, et al. Acad Emerg Med. 2008;15:144-150.

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Types of HIV Screening Tests
Available to Primary Care Providers
● Six rapid HIV tests available
● Results available within 15 to 30 minutes
● 4 are CLIA-waived
- OraSure OraQuick Advance
- Uni-Gold
- Chembio HIV 1/2 Stat-Pak
- Chembio Sure Check
FDA Center for Devices and Radiological Health. Available at:

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCLIA/clia.cfm. Accessed 12-07-07.
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OraQuick:
Oral Fluid, Serum, Whole Blood
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OraQuick:
Results
Positive Negative
Reactive
Control
C C
Positive T
HIV-1 T
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CLIA-Waived HIV Antibody Tests:
Sensitivity and Specificity
Sensitivity Specificity
(95% CI) (95% CI)
OraQuick Advance HIV 1/2
Oral fluid 99.3 99.8
(98.4-99.7) (99.6-99.9)
Whole blood 99.6 100
(98.5-99.9) (99.7-100)
Plasma* 99.6 99.8

(98.9-99.8) (99.6-99.9)
Uni-Gold Recombigen
Whole blood 100 99.7
(99.5-100) (99.0-100)
Serum and plasma* 100 99.8

(99.5-100) (99.03-100)
*Not CLIA waived.
Greenwald JL, et al. Curr Infect Dis Rep. 2006;8:125-131.

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CLIA-Waived HIV Antibody Tests:

(95% CI) (95% CI)
Chembio Stat-Pak HIV 1/2
Whole blood 99.7 99.9
(98.9-100) (99.6-100)
Chembio Sure Check
Whole blood 99.7 99.9
(98.9-100) (99.6-100)

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Non-CLIA-Waived HIV Antibody Tests:

(95% CI) (95% CI)
Reveal G-2
Serum 99.8 99.1
(99.5-100) (98.8-99.4)
Plasma 99.8 98.6

(99.5-100) (98.4-98.8)
Multispot HIV 1/2

Serum 100 99.93
(99.94-100) (99.79-100)
Plasma 100 99.91

(99.94-100) (99.79-100)

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Patient Acceptance of Rapid Testing
● Rapid testing versus “traditional” HIV screening
- Tested at anonymous HIV testing site and STD clinic
- 88% of previously tested preferred rapid results
● Results
- Anonymous testing site
• 4% increase in uninfected and 16% increase in HIV-infected
individuals learning of their serostatus
- STD Clinic
• 210% increase in uninfected and 23% increase in HIV-infected
individuals learning of their serostatus
Kassler WJ, et al. AIDS. 1997;11:1045-1051.

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CDC Revised HIV Screening

Recommendations for Pregnant Women
● Universal opt-out screening
- Included in routine panel of prenatal screening tests
- Notification and option to decline
● Second test in third trimester for women who are
- Known to be at risk for HIV
- In communities with elevated HIV incidence
- In high-prevalence health care facilities
● Labor and delivery opt-out rapid testing for women with
undocumented HIV status
- Initiate antiretroviral prophylaxis on basis of test result
● Rapid testing of newborn if mother’s status unknown at delivery
- Initiate antiretroviral prophylaxis within 12 hours of birth on basis of
rapid test result

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Adolescents:
Special Considerations for HIV Screening
● HIV screening
- Discuss with all adolescents and encourage HIV testing for
those who are sexually active
● Laws concerning HIV testing and confidentiality differ
among states
● Laws and legal precedents allow for evaluation and
treatment of minors for STDs without parental
knowledge or consent
- Not every state has defined HIV infection explicitly as a condition
for which testing or treatment may proceed without parental
consent

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Confirmatory Tests for
Patients Who Test HIV Positive
● Positive rapid antibody tests are considered
preliminary
● Confirmatory testing is needed to diagnose HIV
infection
- ELISA and Western blot test
● HIV-positive test results
- Communicated confidentially through personal
contact by a clinician, nurse, mid-level practitioner,
counselor, or other skilled staff

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National Survey of Family Growth (2002):

Adolescents Who Had Vaginal Sex
80
77%
70
Females
69%
Had Vaginal Sex (%)
60
Adolescents Who
Males
50
40
30
20
10
0
12 15 16 17 18
Age (years)
Mosher WD, et al. National Center for Health Statistics. 2005.

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HIV-Negative Persons:
Prevention Services
● Risk screening
- Assessment of risk for infection with HIV and other
STDs and provision of prevention information should
be incorporated into routine primary care of all
sexually active persons
- Refer at-risk patients to appropriate risk-reduction
services (drug treatment, STD counseling)
● Prevention counseling
- Does not need to be linked to HIV screening
- Should be offered or made available in facilities that
service high-risk populations
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Public Health Issues:
HIV/AIDS Surveillance
● Risk factor assessment
- Recommended in order to target community-wide
prevention efforts
● HIV/AIDS case reporting
- Mandatory reporting of AIDS cases and HIV infection
diagnoses required by all states
● Pediatric exposure reporting
- Recommended by the CDC

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Partner Counseling and Referral

● Encourage patients who test positive for HIV to
notify current and prior sex partners
● Local health departments can make notification
without disclosing patient’s identity
● Providers should notify patients they may be
approached by local health departments for
voluntary interviews regarding partner
notification

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Impact of New Guidelines

on the Health Care System
● Implementation of routine testing
- Dramatically increase funding needs of screening programs,
including the cost of the test itself (conventional or rapid HIV
tests)
● Effective HIV screening programs
- Need to effectively link patients to competent and appropriate
care and prevention services
● Approximately 50% of HIV-positive patients have no
health insurance
- Increased demand on public funding to support the cost of care
and medications
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Summary
● There is a need to increase the proportion of persons
who are aware of their HIV-infection status
- Routine, voluntary, opt-out screening in health care settings is
needed
● Rapid HIV tests
- Provide clinicians with preliminary results in 15 to 30 minutes
● Patients at high-risk for HIV
- Should be counseled on risk reduction strategies
● Treatment and referral services for those who test HIV
positive will benefit patients and society
- Prolong life of HIV-infected individuals
- Likely reduce risk of transmission
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Selecting HAART:
Adherence and Medical Considerations
Brady L. Allen, MD
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What’s New With the DHHS Guidelines

December 1, 2007 January 29, 2008
● When to start antiretroviral therapy ● What to start with
- All patients with CD4 <350 cells/mL - Abacavir/lamivudine now a preferred
- Pregnancy, HIV-associated nephropathy, NRTI (if negative for HLA-B*5701)
hepatitis B cotherapy - Zidovudine/lamivudine changed to
alternative NRTI
● Resistance test at baseline for all
patients - Ritonavir-boosted saquinavir acceptable
for initial therapy, but inferior to
- Whether or not antiretroviral therapy is preferred or alternative PIs
to be started
- Options no longer recommended
● HLA-B*5701 testing prior to the use of • Nelfinavir, stavudine + lamivudine,
abacavir abacavir/zidovudine/lamivudine
● Treatment-experienced patients ● Treatment interruption not

- Integrase inhibitors and CCR5 inhibitors recommended
- Tropism assay recommended before ● Acute HIV
initiating therapy with CCR5 antagonists
● Active or latent TB and HIV infection
Available at: http://aidsinfo.nih.gov/Default.aspx.

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Overview
● When to start treatment
● Treatment goals
● What to start with
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When to Start Treatment

CD4 Cell Count Viral Load 2008 DHHS
Clinical Category (cells/mm3) (copies/mL) Guidelines
AIDS-defining illness or Any value Any value Treat
severe symptoms*
Asymptomatic <200 Any value Treat

200 to 350 Any value Treat
>350 >100,000 Consider treatment
>350 <100,000 Consider treatment in
some patients
Pregnant women Any value Any value Treat

HIV-associated nephropathy Any value Any value Treat
HIV/HBV coinfection when Any value Any value Treat
HBV treatment is indicated
Available at: http://aidsinfo.nih.gov/Default.aspx. Revision January 29, 2008.

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Adherence Considerations
● Concern about adherence to therapy is a major
determinant for timing of initiation of HAART
- Patient readiness is a key factor in future adherence
● No patient should automatically be excluded
from consideration for HAART simply because
the patient may exhibit behaviors or
characteristics affecting adherence

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Potential Benefits and Risks
of Early Therapy
Benefits Risks
● Maintain higher CD4 count and prevent ● Treatment-related side effects and
potentially irreversible damage to the toxicities
immune system ● Development of drug resistance due to
● Decreased risk for HIV-associated incomplete viral suppression
complications - Loss of future treatment options
- Tuberculosis, non-Hodgkin’s ● Less time for patient adjustment to
lymphoma, Kaposi’s sarcoma,
peripheral neuropathy, HPV-associated
disease and treatment requirements
malignancies, and HIV-associated ● Increased total time on medication
cognitive impairment
● Premature use of therapy before
● Decreased risk of nonopportunistic potentially better/safer future options are
conditions available
- Cardiovascular disease, renal disease,
● Transmission of drug-resistant virus in
liver disease, and non–AIDS-associated
malignancies and infections patients who do not maintain full virologic
suppression
● Decreased risk of HIV transmission

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Potential Benefits and Risks

of Early Therapy
Benefits Risks
● Maintain higher CD4 count and prevent ● Treatment-related side effects and
potentially irreversible damage to the toxicities
immune system ● Development of drug resistance due to
● Decreased risk for HIV-associated incomplete viral suppression
complications - Loss of future treatment options
- Tuberculosis, non-Hodgkin’s lymphoma, ● Less time for patient adjustment to
Kaposi’s sarcoma, peripheral neuropathy,
HPV-associated malignancies, and HIV-
disease and treatment requirements
associated cognitive impairment ● Increased total time on medication
● Decreased risk of nonopportunistic ● Premature use of therapy before
conditions potentially better/safer future options
- Cardiovascular disease, renal disease, are available
liver disease, and non–AIDS-associated
● Transmission of drug-resistant virus in
malignancies and infections
patients who do not maintain full
● Decreased risk of HIV transmission virologic suppression

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ART Cohort Collaboration:

Prognosis for Starting HAART
Baseline CD4 Strata
0.4 (cells/mm3)
Probability of AIDS or Death
0-24
0.3 25-49
50-99
0.2
100-199
0.1
200-349
>350
0
0 1 2 3 4 5
Years From Starting HAART
May M, et al. AIDS. 2007;21:1185-1197.

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ATHENA Cohort Study:
Restoring CD4 Count to >800 Cells/mm3
● National observational study Achieving CD4 >800 cells/mm3
- 554 of 5299 previously treatment-
naïve patients were on 1000
>500
uninterrupted HAART for 7 years 900
Median CD4 Cell Count

- Baseline 800 350-500
• CD4: 221 cells/mm3 700 200-350
(cells/mm3)
• HIV RNA: 5.0 log10 copies/mL 600
50-200
● Restoring CD4 >800 cells/mm3 500
- Less time to achieve and a greater 400 <50
proportion achieving with a higher 300
pre-HAART CD4 cell count
200
• >500 cells/mm3: 87%
100 Baseline CD4 Strata
• 350-500 cells/mm3:73% (cells/mm3)
• 200-350 cells/mm3: 46% 0
0 48 96 144 192 240 288 336
• 50 to 200 cells/mm3: 26% Weeks on HAART
Gras L, et al. JAIDS. 2007;45:183-192.

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SMART Study:
Continuous Versus Intermittent HAART
● Open-label study
Rate of Clinical Events
- CD4-guided intermittent therapy 20 Intermittent therapy (n=228)
• Stop: CD4 >350 cells/mm3 Continuous therapy (n=249)
Rate (per 100 person-years)
• Resume: CD4 <250 cells/mm3 16.0

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- Continuous therapy
● Continuous therapy
10.4
10
- 5.7% reduction in absolute risk 9.2
of opportunistic disease and 7.1 7.6
6.7
serious non-AIDS events*
compared with intermittent 5
3.1
therapy
1.8
1.2
0
0
Overall <250 250-349 350-499 >500
Baseline CD4 (cells/mm3)
*CVD, hepatic and renal diseases, non-AIDS cancers and death.
Emery S, et al. 4th IAS Conference. Sydney, 2007. Abstract WePeB018.
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SMART Study: Retrospective Exploratory

Analysis of Cardiovascular Disease Events
CD4-Guided
Intermittent Continuous Relative
Therapy Therapy Hazard
(n=2742) (n=2730) (95% CI)
Number of events
Death from CVD 7 4
Nonfatal clinical MI 12 12
Nonfatal silent MI 11 5
Nonfatal stroke 8 3
CAD requiring surgery or 22 14
invasive procedure
Clinical MI, silent MI, stroke, death from 48 31 1.57*
CVD, CAD requiring invasive procedure (1.00-2.46)
Plus peripheral vascular disease, 76 52 1.49†
CHF, CAD requiring therapy (1.04-2.11)
Plus death from unknown causes 84 54 1.58‡
(1.12-2.22)
*P=0.05; †P=0.03; ‡P=0.009.
Phillips A, et al. 14th CROI. Los Angeles, 2007. Abstract 41.

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Overview
● Treatment goals
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Treatment Goals
● Primary goals
- Reduce HIV-related morbidity and prolong survival
- Improve quality of life
- Restore and preserve immunologic function
- Maximally and durably suppress viral load
- Prevent vertical HIV transmission

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Maximal Viral Suppression

in Initial Therapy
● Use two, preferably three, active drugs from multiple
drug classes
● HIV RNA <50 copies/mL usually occurs within the first
12 to 24 weeks of therapy
● Predictors of virologic success
- High potency of antiretroviral regimen
- Excellent adherence to treatment regimen
- Low baseline HIV RNA level
- Higher baseline CD4 cell count
- Rapid reduction in HIV RNA level in response to treatment
• >1 log10 copies/mL in 1 to 4 months

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Prevalence of
Transmitted Drug Resistance
Europe 2002/2003 (n=1083)
20
18%
USA 2005 (n=240)
17% USA adolescents 2005 (n=55)
15%
15
Resistance (%)
11%
10 9%
7%
5% 5%
5 4% 4%
2% 3%
0
Any Class NRTI NNRTI PI
Wensing AM, et al. J Infect Dis. 2005;192:958-966.

Wensing AM, et al. 16th IAC, 2006. Abstract TuAB0101.
Ross L, et al. 46th ICAAC, 2006. Abstract H-993.
Viani R, et al. J Infect Dis. 2006;194:1505-1509.
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Drug Resistance Testing

● Recommended for all HIV-infected individuals entering
care, regardless of whether therapy will be initiated
- If therapy is deferred, consider repeating testing at the time of
antiretroviral therapy initiation
- Genotypic assay is preferred for treatment-naïve patients
● Recommend genotypic testing
- All pregnant women prior to initiation of therapy
- Those entering pregnancy with detectable HIV RNA levels while
on therapy
● Not advisable when HIV RNA <1000 copies/mL
- Amplification of the virus is unreliable

53
HLA-B*5701 Screening
● Recommended before starting abacavir-
containing regimen
- Reduce the risk of hypersensitivity reaction
● HLA-B*5701 positive
- Avoid abacavir
- Record as abacavir allergy in patient’s medical record
● If HLA-B*5701 screening is not readily available
- Reasonable to initiate abacavir with appropriate
clinical counseling and monitoring for any signs of
hypersensitivity reaction
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Overview
● Treatment goals
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Factors to Consider
When Selecting an Initial Regimen
● Comorbidity or conditions
● Adherence potential
● Dosing convenience and frequency, food and fluid
considerations
● Potential adverse events
● Potential drug interactions
● Pregnancy potential
● Results of genotypic drug testing
● Gender and pretreatment CD4 cell count if considering
nevirapine

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DHHS Guidelines: Preferred Regimens

for Treatment-Naïve Patients
Select 1 NNRTI or 1 PI
Plus a Dual NRTI
NNRTI PI Dual NRTI
Efavirenz1 Atazanavir + ritonavir Emtricitabine/tenofovir DF3
Fosamprenavir + ritonavir bid Abacavir/lamivudine3

(if test negative for HLA-B*5701)
Lopinavir/ritonavir bid2
1Efavirenz is not recommended for use in the 1st trimester of pregnancy or in sexually active women with child-bearing
potential who are not using effective contraception.
2The pivotal study that led to the recommendation of lopinavir/ritonavir as a preferred PI component was based on twice-daily
dosing. A smaller study has shown similar efficacy with once-daily dosing but also showed a higher incidence of moderate
to severe diarrhea with the once-daily regimen.
3Emtricitabine may be used in place of lamivudine and vice versa.

57
19
Pill Burden of
DHHS Preferred HAART Regimens
Pill Food Dosing
Burden Restrictions Frequency
Efavirenz/emtricitabine/tenofovir DF 1 None Once-daily
Efavirenz + emtricitabine/tenofovir DF 2 None Once-daily
Efavirenz + abacavir/lamivudine 2 None Once-daily

Atazanavir + ritonavir + abacavir/lamivudine 4 Yes (ATV) Once-daily
Atazanavir + ritonavir + 4 Yes (ATV) Once-daily

emtricitabine/tenofovir DF
Lopinavir/ritonavir + 5 None Twice-daily (LPV/r)
(emtricitabine/tenofovir DF or Once-daily (NRTI)
abacavir/lamivudine)
Fosamprenavir + ritonavir + 5 None Twice-daily (FPV/r)
(emtricitabine/tenofovir DF or Once-daily (NRTI)
abacavir/lamivudine)

58
DHHS Guidelines: Alternative Regimens

for Treatment-Naïve Patients
Select 1 NNRTI or 1 PI
Plus a Dual NRTI
NNRTI PI Dual NRTI
Nevirapine1 Atazanavir2 Zidovudine/lamivudine3
Fosamprenavir Didanosine + emtricitabine
Fosamprenavir + ritonavir qd Didanosine + lamivudine
Lopinavir/ritonavir qd
Saquinavir + ritonavir
1Nevirapine
should not be initiated in women with CD4 cell count >250 cells/mm 3 or in men with CD4 cell count >400 cells/mm 3
because of increased risk of symptomatic hepatic events in these patients.
2Atazanavir
must be boosted with ritonavir if used in combination with tenofovir.
3Emtricitabine maybe used in place of lamivudine and vice versa.

59
Antiretroviral Treatment Failure

● Often associated with virologic failure, immunologic
failure, and/or clinical progression
● Factors associated with an increased risk of treatment
failure
- Baseline patient factors
- Incomplete medication adherence and missed clinic
appointments
- Drug adverse events and toxicity
- Suboptimal pharmacokinetics
- Suboptimal potency

60
20
Assessing Causes of
Treatment Failure
● Review medical history
- HIV RNA and CD4 cell count change over time
- Occurrence of HIV-related clinical events
- Treatment history
- Results of prior resistance testing
- Adherence issues
- Tolerability of medications
- Concomitant medications and comorbidities
● Assess for signs of clinical progression
61
Assessment of Treatment Failure

● Initial assessment
- Adherence
- Medication intolerance
- Pharmacokinetic issues
- Suspected drug resistance
● Further evaluation
- Incomplete virologic response
• HIV RNA >400 copies/mL after 24 weeks
• HIV RNA >50 copies/mL after 48 weeks
- Virologic rebound
• Repeated detection of HIV RNA above the assay limit of detection

62
General Approaches to the

Management of Virologic Failure
● Goal is to re-establish maximal virologic suppression to a HIV RNA
level of <50 copies/mL
● Identify fully active agents
- Add at least two, and preferably three, fully active agents on the basis
of drug history, resistance testing, or new mechanistic class
- Drug potency and viral susceptibility are more important than the
number of drugs prescribed
- Adding a single, fully active antiretroviral drug is not recommended
• Risk rapid development of resistance
● Discontinuing or briefly interrupting therapy is not recommended
- Increases risk of clinical progression

63
21
Approaches to Improving Adherence
Trevor Hawkins, MD
64
Successful HAART
Clinician experience
Communication skills
Clinician
Replication rate Potency
(Viral load) Pharmacokinetics
Mutation rate Virus Drug (dosage schedule)
(Resistance))
(Resistance
Tolerability
Toxicity
Latent HIV reservoirs Convenience
Patient Resistance
Adherence
Access to care
Access to medication
Life situation
Disease stage
65
Unboosted PI-Regimens
Response and Adherence
HIV RNA <400 copies/mL
100
MEMS cap data
80 78%
Patients (%)
60
45%
40
33%
29%
20 18%
0
95-
95-100 90-
90-94 80-
80-89 70-
70-79 <70
Dose Taken (%)
Paterson DL, et al. Ann Intern Med. 2000;133:21-30.

66
22
Adherence and AIDS-Free Survival
10% Adherence Difference = 21% Reduction in Risk of AIDS
1
Proportion AIDS Free
0.8
0.6
0.4
Adherence (%)
90-100
0.2 50-89
0-49
0
0 5 10 15 20 25 30
Months From Entry
Bangsberg D, et al. AIDS. 2001;15:1181-1183.

67
Time to HAART Discontinuation

by Depressive Symptoms
0.8
Cumulative Survival
Beck Depression Index >15

0.6
0.4
Beck Depression Index <15
0.2
0
0 10 20 30 40 50 60 70
Months on HAART
Bangsberg D, et al. 41st ICAAC. Chicago, 2001. Abstract 1721.

68
Adherence Persepctives
● HIV RNA suppression, reduced rates of
resistance, and improved survival
- Correlated with high rates of adherence to HAART
● Many patients will initiate HAART when
asymptomatic
- The first regimen is the best chance for long-term
success
- Must maintain therapy for a lifetime
● Commitment of lifelong therapy
- By both patient and health care team members
69
23
EuroSIDA (1999-2004):
Changes to First HAART Regimen
● Pooled data from 72
centers across Europe, On First HAART Regimen
100
plus Argentina
- 11,982 patients with 80
70.2% on first HAART
HIV/HCV coinfection
Patients (%)
60
● At the time of starting
HAART
40
- 65.7% treatment-naïve
- 18.1% with AIDS diagnosis 20
● After 1 year, 30% of 0

patients discontinue initial 0 6 12 18 24 30 36 42
Months Since Starting HAART
therapy
Mocroft A, et al. AIDS Res Hum Retroviruses. 2005;21:743-752.
70
Patient Factors Associated with

Poor Adherence in the United States
● Depression
● Active alcohol or drug use
● Low literacy
● Lack of
- Social support
- Belief in the treatment efficacy
● Unstable housing
● Competing priorities
- Housing, childcare, food, work
Available at: http://aidsetc.org/aidsetc?page=cm-302_adhere.
71
Patterns and Predictors of Changes to

HAART: Longitudinal Study (1999-2004)
MACS Cohort WIHS Cohort
Used HAART Used HAART

Completed Adherence Completed Adherence
Questionnaires Questionnaires
1106 men 1624 women
5827 visits 9169 visits
Had Data at Paired Visits Had Data at Paired Visits

812 men 1335 women
5618 visits 6492 visits
Had No Missing Data Had No Missing Data

640 men 1304 women
2803 visit-pairs 5972 visit-pairs
Lazo M, et al. Clin Infect Dis. 2007;45:1377-1385.

72
24
HAART: Patient Characteristics
Demographics Disease Characteristics
Men Women Men Women
(n=640) (n=1304) (n=640) (n=1304)
Age (y) 44.1 38.2* Symptoms of 38 37
Race (%) depression (%)
White 73 15* AIDS (%) 20 40*
Black 19 52 Hospitalizations (%) 8 17*
Hispanic 7 30
HAART (%)
Education less than 3 37* >3 agents 25 15*
high school (%) PI-based 52 47*
Low income (%) 29 37* Both PI + NNRTI 18 12
Health insurance (%) 97 90* PI + NNRTI spared 3 8
Employed (%) 62 68* Undetectable (%) 57 46*
Alcohol use (%) CD4 >350 cells/mm3 (%) 23 22

Binge behavior 7 4* *P<0.01 versus men.
Heavy 15 8
Low 55 28
>2 recreational drugs 27 9*
73

HAART: Full Adherence
● Patients with 100%
Prevalence of 100% Adherence
adherence
100
- Decreased from 91% MACS (P=0.02 for white race)
to 80% between MACS (P=0.93 for Blacks)
WIHS (P=0.54)
1999 to 2004 90
● Maintaining full
Patients (%)
adherence 80
- Was lower among

women and Blacks 70
60
50
6/99 1/00 6/00 1/01 6/01 1/02 6/02 1/03 6/03 1/04 6/04

74
Independent Predictors of
Decreasing Adherence
Odds Ratio (95% CI)
Men Women
(n=640) (n=1304)
Drinking (referent: none)
Binge -- 1.81 (1.20-1.92)
Moderate to heavy -- 1.52 (1.11-2.07)
Low -- 1.29 (1.06-1.57)
Clinical indicators
>2 clinical symptoms 1.38 (1.0-1.92) 1.48 (1.18-1.85)
>1 hospitalizations 1.71 (1.11-2.65) --
Symptoms of depression 1.44 (1.06-1.95) --
Treatment factors
PI-based 1.94 (1.34-2.80) 1.35 (1.11-1.64)
Both PIs and NNRTIs 2.34 (1.45-3.80) --
PI and NNRTI spared 2.41 (1.03-5.61) --
>4 agents -- 1.35 (1.03-1.77)

75
25
Strategies to
Improve Adherence to HAART
● Establish readiness to start therapy
● Provide education on medication dosing
● Review potential side effects
● Anticipate and treat side effects
● Utilize educational aids including pictures, pillboxes, and calenders
● Engage family, friends
● Simplify regimens, dosing, and food requirements
● Utilize a team approach with case managers, nurses, pharmacists,
and peer counselors
● Provide accessible, trusting health care team

76
Assessing Readiness for HAART

● What is your attitude toward HAART?
● Do you believe that HAART is effective?
● What so you hope these medications will do for
you?
● Are you ready to take the medication every day,
around the same time each day?
● Are you committed and motivated to take the
medication every day for the rest of you life?

77
Assessing Readiness for HAART

● Who knows about your HIV status?
● What other medications are you taking?
- Prescription, over-the-counter, herbals?
● Are you a morning or afternoon person?
● What is your daily routine, including waking and bed
times?
● How many meals and snacks do you eat per day, and at
what times?
● Do you use alcohol, marijuana, cocaine, amphetamines,
or injectable drugs?
- If so, how much do you use and how long have you used them?
78
26
Patients Taking HAART
● Do you manage your own medications?
- If not, who manages them for you?
● What HIV medications do you take and what is their
dosage?
- When do you take these?
● How do you remember to take your medications?
● How many doses of your HIV medication have you
missed in the last 72 hours, last week, last 2 weeks, and
last month?

79
Patients Taking HAART

● On a scale of 1 to 10, where would you say you are?
(1: do not take your medicines right at all; 10: take your medications
perfectly every day, at the same time every day)
- If not a 10, what causes you not to be a 10?
- When are you most likely to miss doses?
● Do you have any adverse effects to from your HIV medications?
- If so, what are they?
● Are you comfortable taking medications in front of others?
- What is most difficult about taking your medications?
● How do you like working with your pharmacy?

80
Strategies for
Improving Adherence
● Patients who can identify their medications (in their own words) and
describe the proper dosing and administration have higher
adherence rates
● Providing patient education before writing a prescription helps
ensure adherence to HAART
- Oral, written, or graphic form
• Number of pills, dosages, dosing frequency, dietary restrictions, possible
adverse effects, tips for managing adverse effects
• Success of depends on >95% adherence
● Close follow-up during the first few days of therapy is useful in
identifying adverse effects, assessing the patient's understanding
of the regimen, and addressing any concerns before they become
significant adherence barriers
81
27
Strategies for
Improving Adherence
● Individualized interventions to optimize outcomes for
each patient
● Pharmacists, peer counselors, support groups,
adherence counselors, behavioral interventions, and
community-based case managers are useful in
supporting adherence
● Multidisciplinary teams that include nurses, case
managers, nutritionists, and pharmacists, in which each
care provider focuses on adherence at each contact with
the patient, are extremely effective in supporting
adherence
82
Strategies for
Improving Adherence
● Medication organizers
- Pillboxes and medisets
● Reminder devices
- Alarm watches, beepers, or cell phone alarms
● Medication diaries
● Visual medication schedules
83
HIV/AIDS: Analysis of Case Management

Adherence Training and Coordination
● North Carolina HIV/AIDS case
Barriers to Taking HAART (%)
managers participating in a Clients
Case Management Adherence (n=21)
Training and Coordination Side effects 76.2
Program Depression 57.1
- Perceived role in adherence Anxiety 52.4
- Barriers and strategies to Lack of knowledge about 47.6
providing adherence services disease process
● 9 of 16 case managers Literacy/comprehension 42.9

participated Patient beliefs about knowledge 42.9
Nutrition/lack of food 42.9
- Representing 21 HIV-positive
clients Substance abuse/alcohol and 42.9
street drugs
Lack of support 42.9
Shelton RC, et al. AIDS Patient Care. 2006;20:193-204.

84
28
HIV/AIDS: Analysis of Case Management
Adherence Training and Coordination
● Additional case manager strategies for promoting
adherence coordination following training
- New reminder aids (eg, pill boxes, alarms)
- Work with other health care providers by establishing regular
communication with clients
● Benefits of case management adherence training
- Broadened perceptions of adherence
- Learn more about medications, side effects, and the relationship
between adherence and substance abuse
Shelton RC, et al. AIDS Patient Care. 2006;20:193-204.

85
Efficacy of Interventions in Improving

HAART Adherence and Viral Load
● Meta-analysis
- 19 studies (1996 to 2005) representing 1839 patients
- Impact of behavior interventions addressing HAART
adherence are successful in increasing the likelihood
a patient attains 95% adherence or an undetectable
HIV RNA level
● Results
- Patients receiving intervention were 1.5 times as
likely to report 95% adherence and 1.25 times as likely
to achieve an undetectable HIV RNA
Simoni JM, et al. JAIDS. 2006;43(suppl 1):S23-S35.

86
CPCRA 058 (Adherence Study): Benefit of Long-

Term Antiretroviral Adherence Intervention
● Randomized, adherence
Baseline Characteristics
intervention clinical trial (n=928) Patients
● Adherence interventions (n=928)
- Medication managers Age (y) 38

Gender (%)
• Trained staff member worked
Male 78
individually with patients to
provide tailored adherence Race (%)
support in a standardized Black 55
protocol-guided manner White 25
• Based on health behavior theory Latino 17
Prior IDU (%) 15
- Medication alarms
• Potable alarm to sound and flash Prior AIDS diagnosis (%) 38
at times of all HAART doses CD4 (cells/mm3) 155
● Median follow-up: 30 months HIV RNA (log10 copies/mL) 5.2
Mannheimer SB, et al. JAIDS. 2006;43(suppl 1):S41-S47.

87
29
CPCRA 058 (Adherence Study): Results
● Virologic failure on 2-class HAART
- Significantly lower rates with medication manager group versus
the non-medication manger group
• 28.6 versus 41.2 per 100 person-years (RR: 0.72; P=0.01)
● CD4 cell increase

- Higher increase from baseline in the medication manager group
• Difference between groups 22.5 cells/mm3 (P=0.01)
● Achieving 100% adherence

- Medication manager group had higher rate of patients reporting
100% adherence (OR: 1.42; P<0.001)
Mannheimer SB, et al. JAIDS. 2006;43(suppl 1):S41-S47.

88
Adherence Programs:
Health Care Utilization
● Assessed health care utilization
at public HIV clinics in Los
Rate per 1000
Angeles (11/2001 to 10/2004)
Person-Days
- Baseline IACM DAART SOC
• HIV RNA: 4.28 log10 copies/mL (n=84) (n=82) (n=84)
• CD4: 127 cells/mm3 Hospital 0.6 0.8 0.9
- Mean follow-up: 1.7 years admissions
● Groups Hospital days 2.3 4.2 6.7
- Intensive adherence case Outpatient visits 37.0 44.2 31.5
management (IACM)
Emergency 0.5 0.7 0.7
- Directly administered department visits
antiretroviral therapy (DAART)
- Standard of care (SOC)
Sansom SL, et al. AIDS Patient Care. 2008;22:131-138.

89
Case Management May Reduce

Health Care Utilization Costs
15000 $14,416 IACM (n=84)

DAART (n=82)
$13,127
SOC (n=84)
Cost Per Patient ($)
12000
$9443
$8988
9000
$6851
$6064
6000 $5598
$4766
$3242
3000
0
Total Cost Cost of Cost of
Of Care Hospitalization Outpatient Visits
Sansom SL, et al. AIDS Patient Care. 2008;22:131-138.

90
30
Summary
● Treat patient as a whole
● Adopt a multidisciplinary approach
● Appreciate multicultural differences and needs
● Screen for depression
● Plant the seed of therapy early on
- Antiretroviral therapy is almost never an emergency
● Be honest and reassuring when counseling
● Use practice-management tools
91
Obtaining CE Credits
Attendees are able to evaluate session content and
print CE certificates onsite.
Designated CE stations will be available at the expanded Cyber

Café throughout the conference. You may also access your
personal CE account from any computer with internet access.
Attendees have up to 30-days post conference to evaluate

sessions and print CE certificates.
92
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SY26 The Role of Case Management in Optimzing HIV Treatment

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The Role of Case Management in Optimizing HIV Treatment

Supported by an independent educational

Update this slide

7:35 AM – 7:50 AM Health Benefits of Routine HIV Screening

7:50 AM – 8:10 AM Selecting HAART: Adherence and Medical

8:10 AM – 8:45 AM Approaches to Improving Adherence

9:00 AM – 9:15 AM Question and Answer Session

Contact Hours Statement

CMSA is approved provider of nursing education by the California Board of Registered

Grants/Research None None

Consultant None None

Speaker’s Bureau Abbott Laboratories, Abbott Laboratories, Gilead

Honoraria Abbott Laboratories, Abbott Laboratories, Gilead

Stock Holder None None

Attendees are able to evaluate session content and

Designated CE stations will be available at the expanded Cyber

Attendees have up to 30-days post conference to evaluate

CDC. HIV/AIDS Surveillance Report. June 2007;17. Revised Edition.

Awareness of HIV Serostatus:

Marks G. AIDS. 2006;20:1447-1450.

Reduction in Risk Behaviors

Marks G, et al. JAIDS. 2005;39:446-453.

Duffus W, et al. MMWR. 2006;55(47):1269-1272.

“Late Testers” Account for

HIV Diagnosis (%)

53% 53% 54%

CDC. HIV/AIDS Surveillance Report. June 2007;17. Revised Edition.

National HIV Behavioral Surveillance:

- 83% participation rate 60

- Surveyed about knowledge 20

Branson BM, et al. MMWR Recomm Rep. 2006;55(RR-14):1-17.

Revised CDC Recommendations for

Branson BM, et al. MMWR Recomm Rep. 2006;55(RR-14):1-17.

Opt-Out Versus Opt-In Screening

Branson BM, et al. MMWR Recomm Rep. 2006;55(RR-14):1-17.

Branson BM, et al. MMWR Recomm Rep. 2006;55(RR-14):1-17.

Cost-Effectiveness of Screening the

Paltiel AD, et al. Ann Intern Med. 2006;145:797-806.

Availability of Rapid HIV Testing

Ehrenkranz PD, et al. Acad Emerg Med. 2008;15:144-150.

FDA Center for Devices and Radiological Health. Available at:

Plasma* 99.6 99.8

Serum and plasma* 100 99.8

Greenwald JL, et al. Curr Infect Dis Rep. 2006;8:125-131.

CLIA-Waived HIV Antibody Tests:

Greenwald JL, et al. Curr Infect Dis Rep. 2006;8:125-131.

Non-CLIA-Waived HIV Antibody Tests:

Plasma 99.8 98.6

Multispot HIV 1/2

Plasma 100 99.91

Greenwald JL, et al. Curr Infect Dis Rep. 2006;8:125-131.

Kassler WJ, et al. AIDS. 1997;11:1045-1051.

CDC Revised HIV Screening

Branson BM, et al. MMWR Recomm Rep. 2006;55(RR-14):1-17.

Branson BM, et al. MMWR Recomm Rep. 2006;55(RR-14):1-17.

Branson BM, et al. MMWR Recomm Rep. 2006;55(RR-14):1-17.

National Survey of Family Growth (2002):

Mosher WD, et al. National Center for Health Statistics. 2005.

Branson BM, et al. MMWR Recomm Rep. 2006;55(RR-14):1-17.

Partner Counseling and Referral

Branson BM, et al. MMWR Recomm Rep. 2006;55(RR-14):1-17.

Impact of New Guidelines