HIV Treatment Guidelines:
Reviewing Essentials for Optimal Care
Sponsored for CME credit by Supported by an independent educational
Rush University Medical Center grant from Gilead Sciences Medical Affairs
Educator
The Very Rev. Father Drew A. Kovach, MD, MDiv.
Director of HIV Services
Kaiser Permanente Hawaii
2
Accreditation and Designation
Rush University Medical Center is accredited by the Accreditation Council for
Continuing Medical Education to provide continuing medical education for physicians.
Rush University Medical Center designates this educational activity for a maximum of
1 AMA PRA Category 1 Credit™. Physicians should only claim credit commensurate
with the extent of their participation in the activity.
The Association of Nurses in AIDS Care (ANAC) is an approved provider of
continuing education in nursing by the Virginia Nurses Association Continuing
Education Approval Committee, an accredited approver by the American Nurses
Credentialing Center’s Commission on Accreditation.
The University of Florida College of Pharmacy is accredited by the Accreditation
Council for Pharmacy Education as a provider of continuing pharmacy education
(UPN #012-999-07-206-L02-P). This slide kit is accredited for one hour of continuing
education credit. The University of Florida College of Pharmacy will mail Statements of
Continuing Education Credit within 30 working days after receiving evidence of
successful completion of the course. Successful completion means that you must
attend the entire program and complete an evaluation form.
This program is accredited for case managers through the Commission for Case
Manager Certification (CCMC). To have clock hours added to your certification file,
please submit the verification of completion form provided by your host directly to
CCMC.
Supported by an independent educational grant from Gilead Sciences Medical Affairs.
3
Faculty:
CME Course Director
Harold A. Kessler, MD
Professor of Medicine and Immunology/Microbiology
Associate Director, Section of Infectious Diseases
Rush University Medical Center
Chicago, Illinois
4
Faculty:
Content Development and Training
Renslow D. Sherer, MD
Clinical Associate
Section of Infectious Disease
The University of Chicago
Director, Infectious Disease Unit
Project HOPE
Chicago, Illinois
5
Disclosure Information
● It is the policy of the Rush University Medical Center Office of Continuing
Medical Education to ensure that its CME activities are independent, free of
commercial bias and beyond the control of persons or organizations with
an economic interest in influencing the content of CME
● Everyone who is in a position to control the content of an educational
activity must disclose all relevant financial relationships with any
commercial interest (including but not limited to pharmaceutical
companies, biomedical device manufacturers, or other corporations whose
products or services are related to the subject matter of the presentation
topic) within the preceding 12 months
● If there are relationships that create a conflict of interest, these must be
resolved by the CME Course Director in consultation with the Office of
Continuing Medical Education prior to the participation of the faculty
member in the development or presentation of course content
6
Disclosure Information:
CME Course Director
● Harold A. Kessler, MD
- Grants/Research Support
• Boehringer Ingelheim, Gilead Sciences, Merck, Tibotec,
Theratechnologies
- Consultant
• Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Tibotec, Virco
- Speakers’ Bureau
• Bristol-Myers Squibb, GlaxoSmithKline, Merck, Tibotec, Virco
- Stock Shareholder
• Abbott Laboratories, GlaxoSmithKline, Merck
- Other Financial or Material Support: none
7
Disclosure Information:
Content Faculty
● Renslow D. Sherer, MD
- Grants/Research Support
• Abbott Laboratories, Johnson & Johnson, Pfizer
- Consultant
• Abbott Laboratories, GlaxoSmithKline, Tibotec
- Speakers’ Bureau
• Abbott Laboratories
- Stock Shareholder
• None
- Other Financial or Material Support
• None
8
Disclosure Information:
Medical Writer
● Peter Pinkowish
- Grants/Research Support
• None
- Consultant
• None
- Speakers’ Bureau
• None
- Stock Shareholder
• None
- Other Financial or Material Support
• None
9
Disclosure Information:
Educator
● Drew A. Kovach, MD, MDiv.
- Grants/Research Support
• None
- Consultant
• Gilead
- Speakers’ Bureau
• Gilead, BMS, Merck, Monogram Biosciences
- Stock Shareholder
• None
- Other Financial or Material Support
• None
10
Opinions and Off-Label Discussions
The opinions or views expressed in this educational program are
those of the participants and do not necessarily reflect the opinions
or recommendations of Gilead Sciences Medical Affairs,
Rush University Medical Center, University of Florida College of
Pharmacy, Association of Nurses in AIDS Care, or
Commission for Case Manager Certification
The faculty may have included discussion on unlabeled uses
of a commercial product or an investigational use of a
product not yet approved for this purpose
Please consult the full prescribing information before using
any medication mentioned in this program
11
Program Evaluation
Your feedback is essential for measuring
the success of this CME/CE program
Completion of the program evaluation, included within your
materials, and submission to the onsite program Host is required
CME/CE credits for this program cannot be provided
without a completed evaluation
A post-activity brief online survey will be e-mailed to you in
4 to 8 weeks to assess how your participation in this
educational activity has affected your practice of medicine
12
Slide Handouts
● The enclosed slide handouts are provided for
reference purposes only
● The faculty presenter may have customized the
slides through reordering or deleting and thus
the handouts may not exactly match the
presentation
13
Learning Objectives (CME, CE, CPE)
● At the completion of this educational activity,
participants should be able to:
- Explain the current recommendations on when to
initiate antiretroviral therapy defined by the
Department of Health and Human Services (DHHS)
guidelines
- Describe the efficacy and safety data from key clinical
trials on preferred initial antiretroviral regimens
recommended by the DHHS guidelines
- Explain what constitutes treatment failure and review
treatment considerations when a change in therapy is
warranted
14
A Brief History of
Antiretroviral Therapy
● Early 80’s
- No antiretroviral therapy
● Late 80’s
- Zidovudine monotherapy
● Early 90’s
- Sequential NRTI monotherapy and dual-NRTI therapy
● Late 90’s
- The early HAART era
● Early 00’s
- Trials of treatment interruption
● Late 00’s
- Earlier initiation of therapy
- More potent, durable regimen combinations
- New classes of therapy
15
What’s New With the DHHS Guidelines
January 29, 2008 November 3, 2008
● What to start with ● What to start with
- Abacavir/lamivudine now a preferred - Abacavir/lamivudine now an alternate
NRTI (if negative for HLA-B*5701) NRTI due to concerns about increased
- Zidovudine/lamivudine changed to risk of myocardial infarction and
alternative NRTI virologic potency in patients with
baseline HIV RNA >100,000 copiers/mL
- Ritonavir-boosted saquinavir acceptable
for initial therapy, but inferior to - Ritonavir-boosted darunavir and once-
preferred or alternative PIs daily lopinavir/r are now preferred PIs
- Options no longer recommended - Use with caution
• Nelfinavir • Nevirapine + tenofovir DF + emtricitabine
(or lamivudine)
• Stavudine + lamivudine
- Options no longer recommended
• Abacavir/zidovudine/lamivudine
• Unboosted atazanavir + didanosine +
● Treatment interruption emtricitabine (or lamivudine)
- Long-term treatment interruption not ● Resistance testing recommended for
recommended baseline HIV RNA 500-1000 copies/mL
Available at: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.
Revision November 3, 2008.
16
Program Overview
● When to start treatment
● Treatment goals
● What to start with
● Assessing treatment failure and when to change
17
When to Start Treatment
CD4 Cell Count Viral Load 2008 DHHS 2008 IAS-USA
Clinical Category (cells/mm3) (copies/mL) Guidelines Guidelines
AIDS-defining illness Any value Any value Treat
or severe symptoms*
Asymptomatic 350 >100,000 Consider treatment
>350 500 Cells/mm3
● Determine impact of Baseline Characteristics
initiating HAART at Initiate Defer
CD4 >500 cells/mm3 on HAART HAART
predicted survival (n=2616) (n=6539)
Male (%) 82 83
● Treatment arms Age (years) 40 38
- Initiate treatment with HIV RNA (log10 copies/mL) 3.6 3.7
CD4 >500 cells/mm3 Median CD4 (cells/mm3) 660 664
- Deferred treatment when HCV coinfection (%) 25 35
CD4 decreases to 500 Cells/mm3
Relative Hazard
(95% CI) P Value
Deferral of HAART with CD4 1.6 500 cells/mm3 (1.3, 1.9)
Female sex 1.2 0.117
(0.9, 1.6)
Older age (per 10 years) 1.6 350 cells/mm3 Continuous therapy (n=2752)
Rate (per 100 person-years)
• Resume: CD4 500
therapy Latest CD4 (cells/mm3)
SMART Study Group. J Infect Dis. 2008;197:1145-1155.
24
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.
25
D:A:D Study: Risk of MI Per Exposure
to Individual NRTIs, PIs, and NNRTIs
NRTIs PIs and NNRTIs
(Recent and Cumulative Exposure) (Cumulative Exposure)
Recent exposure (yes/no)
Cumulative exposure
(per year)
Relative Risk (95% CI)
Relative Risk (95% CI)
ZDV ddI d4T 3TC ABC TDF IDV NFV LPV/r SQV NVP EFV
Number of Number of
P-Y FU: 138,109 74,407 95,320 152,009 53,300 39,157 P-Y FU: 68,469 56,529 37,136 44,657 61,655 58,946
No. of MIs: 523 331 405 554 221 139 No. of MIs: 298 197 150 221 228 221
Adjusted for baseline demographics and cardiovascular risk factors and for latest measures of lipids, metabolic parameters,
CD4 count, and HIV RNA level. P-Y FU: patient-years follow-up.
Recent use: current or within the last 6 months.
Lundgren J, et al. 16th CROI. Montreal, 2009. Abstract 44LB.
26
D:A:D Study:
Conclusions
● Abacavir, didanosine, indinavir, and lopinavir/ritonavir
were associated with an increased risk of MI
- For indinavir and lopinavir/r
• Risk increased with cumulative exposure
● No significant associations between exposure to other
NRTIs including tenofovir DF, NRTIs, or the other PIs
and the risk of MI
● Concomitant use of ritonavir did not appear to modify
the effects of saquinavir or indinavir
Lundgren J, et al. 16th CROI. Montreal, 2009. Abstract 44LB.
27
Liver Disease is the Second Leading Cause
of Death in HIV-Infected Patients (1999-2004)
● D:A:D study (n=23,441)
Cause of Death (n=1246)
- Median follow-up: 3.5 years
● Baseline characteristics
- Nadir CD4: 200 cells/µL 31.1%
- Previous AIDS: 26.5%
Patients (%)
- HCV positive: 22.5%
- Active HBV infection: 6.8%
• Inactive HBV infection: 21.4%
14.5%
- Receiving combination antiretroviral
11.0%
therapy: 88.7%
● Mortality
- Total: 5.3%
- Incidence: 1.62 per 100 person-years AIDS Liver-Related CVD
Diseases
- Median age: 44 years
Weber R, et al. Arch Intern Med. 2006;166:1632-1641.
28
Independent Predictors
of Liver-Related Death
Latest CD4 Cell Count (cells/µL) 16.06
500
2.01
HIV Acquisition via IDU
Hepatitis C Status
Negative
6.66
Positive
Hepatitis B Status
Negative
3.73
Positive
0.2 1.0 10 100
Multivariate analysis. Relative Rate of Death
Not shown: Age per 5 years (1.32).
Weber R, et al. Arch Intern Med. 2006;166:1632-1641.
29
HOPS Cohort: Early Initiation of
HAART Decreases Risk of Toxicities
● Prospective, dynamic
cohort (>8000 patients) Peripheral Renal
- 8-year follow-up Neuropathy Anemia Insufficiency
(n=1969) (n=1398) (n=1152)
● Incidence of nucleoside Number of 294 70 79
analogue-associated incident
cases
toxicities was significantly
Hazard Ratio (95% CI)
reduced when HAART was
Pre-HAART CD4
initiated at progressively cell count (cells/mm3)
higher CD4 cell counts 0-199* 1.43† 1.34 2.23‡
(1.05-1.93) (0.77-2.32) (1.22-4.06)
● These data suggest that a
>350* 0.88 0.63 1.01
delay in initiating HAART (0.64-1.21) (0.33-1.21) (0.52-1.94)
increases the risk of Multivariate analysis.
toxicities *Referent to CD4 cell count 200 to 349 cells/mm3.
†P=0.022.
‡P=0.009.
Lichtenstein KA, et al. JAIDS. 2008;47:27-35.
30
Program Overview
● When to start treatment
● Treatment goals
● What to start with
● Assessing treatment failure and when to change
31
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
Available at: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.
Revision November 3, 2008.
32
Maximal Viral Suppression
in Initial Therapy
● Use two, preferably three, active drugs from multiple
drug classes
● HIV RNA 1 log10 copies/mL in 1 to 4 months
Available at: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.
Revision November 3, 2008.
33
Strategies to Achieve Treatment Goals
● Selection of initial combination regimen tailored to the
patient
- Efficacy, pill burden, potential side effects
● Pretreatment drug resistance testing
● Improve potential for adherence
- Simplify medication regimens
- Address patient factors (eg, active substance abuse, depression)
- Discuss health system issues (eg, interruptions in medication
access
- Inadequate treatment education and support
Available at: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.
Revision November 3, 2008.
34
Prevalence of
Transmitted Drug Resistance
Europe 2002/2003 (n=1083)
18%
USA 2005 (n=240)
17% USA adolescents 2005 (n=55)
15%
Resistance (%)
11%
9%
7%
5% 5%
4% 4%
2% 3%
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.
35
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
● Recommended when HIV RNA 500 to 1000 copies/mL
- Amplification of the virus may not be reliable
Available at: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.
Revision November 3, 2008.
36
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
Available at: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.
Revision November 3, 2008.
Hammer SM, et al. JAMA. 2008;300:555-570.
37
Program Overview
● When to start treatment
● Treatment goals
● What to start with
● Assessing treatment failure and when to change
38
DHHS Guidelines Recommendations
for Treatment-Naïve Patients
Select 1 NNRTI or 1 PI Plus a Dual NRTI
NNRTI PI Dual NRTI
Preferred Efavirenz1 Atazanavir + ritonavir qd2 Emtricitabine/tenofovir DF
Darunavir + ritonavir qd
Fosamprenavir + ritonavir bid
Lopinavir/ritonavir qd or bid3
Alternative Nevirapine4 Atazanavir5 Abacavir/lamivudine6
Fosamprenavir Zidovudine/lamivudine
Fosamprenavir + ritonavir qd Didanosine + emtricitabine
Saquinavir + ritonavir Didanosine + lamivudine
1Do not use during 1st trimester of pregnancy or in those with high pregnancy potential. Use with caution in patients with
unstable psychiatric disease.
2Do not use in patients who require high-dose (>20 mg omeprazole equivalent/day) proton-pump inhibitors (PPIs). Use with
caution in patients on PIIs on any dose, H2 blockers, or antacids.
3Do not use lopinavir/r once-daily in pregnant women.
4Do not use in patients with severe hepatic impairment (Child-Pugh score B or C) and in women with CD4 cell count >250
cells/mm3 or in men with CD4 cell count >400 cells/mm3.
5Do not use in combination with tenofovir DF or didanosine/lamivudine.
6Do not use in patients who test positive for HLA-B*5701. Use with caution in patients with baseline HIV RNA
>100K copies/mL and in patients at high risk for cardiovascular disease.
Available at: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.
Revision November 3, 2008.
39
IAS-USA Guidelines Recommendations
for Treatment-Naïve Patients
Select 1 NNRTI or 1 PI Plus a Dual NRTI
NNRTI PI Dual NRTI
Preferred Efavirenz Lopinavir + ritonavir Emtricitabine/tenofovir DF1
Atazanavir + ritonavir Abacavir/lamivudine2
(if test negative for HLA-B*5701)
Fosamprenavir + ritonavir
Darunavir + ritonavir
Saquinavir + ritonavir
Alternative Nevirapine Zidovudine/lamivudine
Didanosine + emtricitabine
Didanosine + lamivudine
1A baseline urinalysis and estimation of creatinine clearance or glomerular filtration rate for assessment of renal function are
recommended. All patients receiving tenofovir should be observed for development of renal dysfunction. Lamivudine can be
substituted for emtricitabine.
2Emtricitabine can be substituted for lamivudine.
Hammer SM, et al. JAMA. 2008;300:555-570.
40
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
Available at: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.
Revision November 3, 2008.
41
DHHS Guidelines Recommendations:
Dual NRTI Components
● Preferred
- Emtricitabine/tenofovir DF*
● Alternative
- Abacavir/lamivudine* (if negative for HLA-B*5701)
- Zidovudine/lamivudine*
- Didanosine + lamivudine or emtricitabine
*Emtricitabine may be used in place of lamivudine or visa versa.
Available at: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.
Revision November 3, 2008.
42
D:A:D Study: Risk of MI Per Exposure
to Individual NRTIs, PIs, and NNRTIs
NRTIs PIs and NNRTIs
(Recent and Cumulative Exposure) (Cumulative Exposure)
Recent exposure (yes/no)
Cumulative exposure
(per year)
Relative Risk (95% CI)
Relative Risk (95% CI)
ZDV ddI d4T 3TC ABC TDF IDV NFV LPV/r SQV NVP EFV
Number of Number of
P-Y FU: 138,109 74,407 95,320 152,009 53,300 39,157 P-Y FU: 68,469 56,529 37,136 44,657 61,655 58,946
No. of MIs: 523 331 405 554 221 139 No. of MIs: 298 197 150 221 228 221
Adjusted for baseline demographics and cardiovascular risk factors and for latest measures of lipids, metabolic parameters,
CD4 count, and HIV RNA level. P-Y FU: patient-years follow-up.
Recent use: current or within the last 6 months.
Lundgren J, et al. 16th CROI. Montreal, 2009. Abstract 44LB.
43
D:A:D Study:
Conclusions
● Abacavir, didanosine, indinavir, and lopinavir/ritonavir
were associated with an increased risk of MI
- For indinavir and lopinavir/r
• Risk increased with cumulative exposure
● No significant associations between exposure to other
NRTIs including tenofovir DF, NRTIs, or the other PIs
and the risk of MI
● Concomitant use of ritonavir did not appear to modify
the effects of saquinavir or indinavir
Lundgren J, et al. 16th CROI. Montreal, 2009. Abstract 44LB.
44
Abacavir and CVD Risk:
Summary of Key Studies/Analyses
Effect of
Study Event Abacavir Found
Design Assessment on CVD Risk
D:A:D (n=33,347) Prospective, Prospective, Yes
observational cohort predefined
French Hospital Case control in Prospective Yes
Database (n=289 cases; observational cohort (validated (1styear of
884 controls) retrospectively) exposure)
SMART (n=2752) Randomized control trial, Prospective, Yes
observational analysis predefined
STEAL (n=357) Randomized control trial Prospective Yes
GSK analysis (n=14,174) Randomized control Retrospective, No
trials (n=54) database search
ACTG 5001/ ALLRT Randomized control Retrospective No
(n=3205) trials (n=5)
Reiss P. 16th CROI. Montreal, 2009. Abstract 152.
45
DHHS Guidelines Recommendations:
NNRTI or PI Components
● Preferred
- Efavirenz*
- Atazanavir + ritonavir
- Darunavir + ritonavir
- Fosamprenavir + ritonavir bid
- Lopinavir/ritonavir qd or bid
● Alternative
- Nevirapine (females and males with CD4 3 antiretrovirals 3 antiretrovirals
Triple-NRTI High rate of early virologic non- Abacavir/zidovudine/lamivudine
regimens response with ABC/TDF/3TC or Possibly tenofovir DF + zidovudine/
TDF/ddI/3TC lamivudine
Other triple-NRTI regimens have
not been evaluated
Available at: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.
Revision November 3, 2008.
48
Antiretroviral Components That
Should Not Be Offered At Any Time
Rationale Exception
Atazanavir + Potential additive hyperbilirubinemia No exception
indinavir
Didanosine + High incidence of toxicities When no other antiretroviral options
stavudine Serious, even fatal cases of lactic acidosis are available and potential benefits
with hepatic steatosis + pancreatitis in outweigh the risks
pregnant women
2 NNRTI High incidence of adverse events, drug No exception
combinations interaction (reduced efavirenz levels)
Emtricitabine + Similar resistance profile No exception
lamivudine No potential benefit
Nelfinavir in Ethyl methanesulfonate, known No exception
pregnant women animal carcinogen, mutagen,
and teratogen
Stavudine + Antagonistic effect on HIV No exception
zidovudine
Available at: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.
Revision November 3, 2008.
49
Program Overview
● When to start treatment
● Treatment goals
● What to start with
● Assessing treatment failure and when to change
50
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
Available at: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.
Revision November 3, 2008.
51
Switching Treatments on One or More
Occasions Becomes Necessary
Reason for Changing First HAART (1999-2003)
30.4% 30.2%
Patients (%)
17.9%
13.7%
7.8%
Failure Toxicities Choice Other Unknown
n=1198 HIV/HCV-coinfected patients; overall rate for stopping: 31.1%.
Mocroft A, et al. AIDS Res Hum Retroviruses. 2005;21:527-536.
52
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
Available at: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.
Revision November 3, 2008.
Hammer SM, et al. JAMA. 2008;300:555-570.
53
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
Available at: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.
Revision November 3, 2008.
Hammer SM, et al. JAMA. 2008;300:555-570.
54
Assessment of Virologic Failure
● No consensus on the optimal time to change therapy for
virologic failure
- Aggressive approach
• Change for any repeated, detectable viremia after suppression to
HIV RNA 1000 copies/mL
- Ongoing replication promotes selection of drug resistance and may
limit future options
● Assess degree of drug resistance and consider prior
treatment history and prior resistance results
Available at: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.
Revision November 3, 2008.
Hammer SM, et al. JAMA. 2008;300:555-570.
55
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
Available at: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.
Revision November 3, 2008.
Hammer SM, et al. JAMA. 2008;300:555-570.
56
Program Evaluation
Your feedback is essential for measuring
the success of this CME/CE program
Completion of the program evaluation, included within your
materials, and submission to the onsite program Host is required
CME/CE credits for this program cannot be provided
without a completed evaluation
A post-activity brief online survey will be e-mailed to you in
4 to 8 weeks to assess how your participation in this
educational activity has affected your practice of medicine
57
Outcomes Measurement Reminder
● CME providers are required to assess “changes in
learners competence, performance or patient outcomes
achieved as a result of their participation in a CME
sponsored educational activity”
● As a result of this requirement you will receive via e-mail
a short 1-page survey 1 to 3 months after completing
this course
- We consider the survey to be an additional component of your
overall participation in this educational activity and would urge
you to reflect on what you learned in the activity and then
complete this survey
● Please be certain that you have correctly written your
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complete at the end of today’s activity
58
Comprehensive Care
of HIV Patients
● My Approach
● The Art of Medicine and application of
Science to the individual when treating
HIV patients
CONCEPTS OF WHOLENESS &
WELLNESS – MY BIAS
● Whole people
- Body
- Mind
- Spirit
● Whole lives
● Levels of Healing
● Life being livable not just being alive
● A good life
HIV/AIDS
● The most comprehensive chronic disease
● Impacts all aspects of a person’s life
- Social
- Economic
- Physical
- Emotional
- Spiritual
With an uncertain future…
Holistic Approach
● Mind, Body, Spirit – The “trinity” of man
● 3 Spheres
● Dis-ease, distress or pain in any one affects the
other two
● Managing whole people to make people whole
Treat the Whole Person
● Not just treating numbers or lab values
● Not just treating with pills
● Not just treating only the symptoms
● Not just treating stereotypes
● Not just treating to make ourselves feel better
● Not just treating the mind and the body
Quality &
Quantity of Life
Access the Patient and Ourselves
● Meeting people “on the road” where they are,
not where we think they should be
● Admit our own bias and prejudice and
frustration
● Admit that how we feel will affect how we treat
EMOTIONAL ISSUES
OF HIV
Emotional Issues of HIV
● “Heart ache” vs. Chest Pain
● “Who is on your back” vs. Back Pain
● “Worn out” vs. Fatigue
● Relationship
- With yourself
- With others
- With God
Emotional Issues of HIV
● Partner Issues (past, present, future)
- One partner positive, the other negative
- Both positive
- No partner
● Parents and Family Issues (past, present,
future)
● Friends and co-worker Issues (past, present,
future)
Emotional Issues of HIV
● Financial Issues (past, present, future)
● Job Issues
- Feeling of self-worth, “pulling your own weight”
- Identity
- Common ground with others. “What do you do?”
Emotional Issues of HIV
● Living with a chronic potentially fatal disease, in
otherwise young healthy people, with an
uncertain future
● “Pill Burden”
- Number (PI vs. NNRTI regimens)
- Timing (complex regimens)
- Constant reminder
Looking Good, Feeling Bad
The disconnect…
Emotional Issues of HIV
● The “Follow-up” Burden
- Frequent labs and other tests
- Frequent office visits
- Multiple sources of treatment and care
- Refilling prescriptions
Emotional Issues of HIV
● The Burden of not feeling “normal”
- Effects of the disease
- Effects of the treatments
- We ask our patients to “get used to” not feeling well
and to tolerate “side effects”
● The Burden of not looking “normal”
- Lipodystrophy and wasting syndrome
Emotional Issues of HIV
● No end to the therapy in sight
● The uncertain future
- of successful therapy?
- of long term side effects from the therapy?
Emotional Issues of HIV
● HIV vs. Cancer Model
- Cyclic vs. Continuous chemotherapy
- How long will the remission last?
- What do I do if and when “it comes back?”
- Do I even want to treat it?
- Will you help me with the pain?
The Result of Emotional Issues of HIV
● ANXIETY and DEPRESSION
- “The Twins” Never separate
- All individual with HIV will become
clinically depressed; early, middle or late
but it will come!
- Patient & doctor need to recognize it
- Tools: Anxiety and depression inventories
(Beck, Hamilton etc.)
The Treatment of the Emotional Issues
of HIV
● Treat or Refer; But Do Something!
● Anti-anxiety agents
● Antidepressants
● Psychotherapy
- Individual
- Group
The Treatment of the Emotional Issues
of HIV
● Behavioral Therapies
- Hypnosis
- Biofeedback
- Jacobson Progressive Relaxation
- Cognitive Behavioral Management
SPIRITUAL ISSUES
OF HIV
What Is Spirituality?
It is NOT Religion!
Religion
● Rituals
● Rules
● Collective
● Control
● Mind
● Belief
● Vehicle to things spiritual
● Think “from the outside in”
Spirituality
● Experience
● Imagination
● Freedom
● Soul
● Personal
● Think “from the inside out”
WHAT THEN IS IT?
● It is core
● It is essence
● It is inspiration
● IT IS LIFE
Soul as in Sol.
Sol as in Sun.
Sun as in Light.
Spiritual Sources
● The patient
● The provider
● The partner/spouse
● The family
● The community of faith
● The cosmos
● The God or Creator
Spiritual Issues of HIV
● Purpose of life
● Beyond ourselves
● “Hole” in the heart
● Guilt and Judgment
● Suffering
● Relationships with people and with God
Spiritual Issues of HIV
● Guilt about lifestyle choices
● “Judgmental” churches
● No support for gay, lesbian, bisexual, &
transgender people
● No support of same sex relationships
● Guilt and judgment about having HIV
The Result of Spiritual Issues
of HIV
● Feeling abandoned by God
● Feeling a sense of condemnation
● Feeling alienated from “religious people”
● Feeling helpless and hopeless
● Feeling worthless
● Feeling sad
● Feeling bad
Treatment of Spiritual Issues
of HIV
● Treat or Refer; But Do Something!
● Acknowledge that these issues are real
● Pastoral care to find Spiritual peace
● Tolerant, inclusive congregations
● The Sacraments (Religious “Actions”)
- The Mass, Divine Liturgy, Communion
- Confession: Forgiveness & Absolution
- Anointing with Prayers for Healing
● Prayer and Meditation
Treatment of Spiritual Issues
of HIV
● Inspirational books and articles
● Inspirational writings by people living with HIV
● Websites
● Spiritual support groups
● My Prescription for Spiritual Wellness
Prescription for
Spiritual Wellness
● Meaning in life involves finding the greatness
hidden inside of us.
● Purpose in life is determined by how we use this
greatness.
● Faith is to believe that greatness can be
embedded within the frailty of our own fallibility.
Prescription for
Spiritual Wellness
● Serenity involves using our goodness to
pursue meaning until moments of
greatness reveal themselves to us.
● Courage is to recognize moments of
greatness when they occur, despite
personal cost.
● Dissonance lingers in the state of unvisited
expectations of greatness.
Prescription for
Spiritual Wellness
● Grace is to understand that our greatness
does not belong to us, simply because it is
inside of us.
● Perspective is gained with understanding that
greatness does not extinguish or diminish
with passing of time or opportunity.
Prescription for
Spiritual Wellness
● Wisdom is approached when we
understand that we do not have the
latitude to choose which greatness is ours
or how large our greatness is.
● Simplicity involves not trying to make
someone else’s greatness our own.
● Power in life is revealed when we
recognize greatness hidden inside of
every being.
Prescription for
Spiritual Wellness
● Joy resides in appreciation of the
greatness of others.
● Love is discovered when we help another
find their greatness and to accept their
help in finding ours.
● Peace in life occurs when we recognize
that regardless of whether we discover
our greatness we are still loved by our
Creator/God.
All Issues Of HIV
Has To Be Managed
● Spiritual
● Emotional
● Physical
- Making people whole requires a holistic
approach
- Wellness
- Wholeness
- Holiness
In their words…
David Taylor
Tom Connor
Linda Jordan
Joel Arce, Luis Arce, Angel
Glover, Steve Koceja and
Noel Arce
Daniel Waters
Diana Hindrew
All God’s Blessings
Thank you