THE CHALLENGE OF STARTING HAART IN CORRECTIONS

1
THE CHALLENGE OF STARTING HAART IN CORRECTIONS

• Ernesto J. Lamadrid, MD, AAHIVS
• Florida/Caribbean AETC
• August 11, 2007

2
Disclosure of Financial Relationships

• This speaker has no significant financial
  relationships with commercial entities to
  disclose.

This slide set has been peer-reviewed to ensure
that there are no conflicts of interest
represented in the presentation.
3
The Human Immunodeficiency Virus
4
Adults and children estimated to be living with
HIV, 2005
Eastern Europe Central Asia 1.5 million 1.0
2.3 million
Western Central Europe 720 000 550 000 950
000
North America 1.3 million 770 000 2.1 million
East Asia 680 000 420 000 1.1 million
North Africa Middle East 440 000 250 000 720
000
Caribbean 330 000 240 000 420 000
South South-East Asia 7.6 million 5.1 11.7
million
Sub-Saharan Africa 24.5 million 21.6 27.4
million
Latin America 1.6 million 1.2 2.4 million
Oceania 78 000 48 000 170 000
Total 38.6 (33.4 46.0) million
UNAIDS
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Incarceration and HIV/AIDS

• Incarcerated in USA
• 1,310,710 in state and federal prison
• Prevalence of HIV
• 2.2 of state prison inmates
• 3.6 of female state prison inmates
• 1997 20 to 26 of people living with HIV in the
  USA passed through a correctional facility
• Prevalence of AIDS
• 0.6 of state inmates
• 0.2 of federal inmates
• Overall rate of AIDS among prison inmates 4x that
  in the general population

Maruschak LM. Bureau of Justice Statistics
Bulletin. 2000. NCJ 196023. Hammett TM, et al. Am
J Public Health. 2002921789-1794.
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US HIV DataPrisons and General Population

• State and federal prisons (2004)
• HIV prevalence among the prison population was 4
  to 5 times that of the general population
• 1.8 of inmates known to be HIV positive
  (n23,046)
• Males 1.7 (n20,668)
• Females 2.4 (n2084)

HIV Prevalence
All Prisoners(State and Federal)
Prevalence ()
General Population
Estimated. Reported.
98 99 00 01 02 03
04
Year
Maruschak LM. Bur Justice Stat Bull. November
2006. Available at http//www.ojp.usdoj.gov/bjs/a
bstract/hivp04.htm.
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Identified HIV InfectionDistribution by
Jurisdiction (2004)
14.1 Florida (n3250)
10.4 Texas (n2405)
California (n1212)
19.5 New York (n4500)
5.3
Georgia (n1109)
4.8
45.9 Other State and Federal Prisons (n10,570)
Maruschak LM. Bur Justice Stat Bull. November
2006. Available at http//www.ojp.usdoj.gov/bjs/a
bstract/hivp04.htm.
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US AIDS DataPrisons and General Population

• State and federal prisons (2004)
• Overall rate of confirmed AIDS among the prison
  population was gt3 times that of the general
  population
• Inmates 0.5
• General population 0.15

Confirmed AIDS Cases
All Prisoners(State and Federal)
Cases per 10,000
General Population
93 94 95 96 97 98 99 00 01 02 03 04
Year
Maruschak LM. Bur Justice Stat Bull. November
2006. Available at http//www.ojp.usdoj.gov/bjs/a
bstract/hivp04.htm.
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Why Care About the Healthof Inmates?

• Those who have been incarcerated
• 25 of HIV-infected Americans
• 33 of Americans infected with hepatitis C virus
  (HCV)
• 40 of Americans with active tuberculosis
• Among inmates
• Up to 50 have axis 1 or 2 mental disorders
• As many as 75 have alcohol and/or other
  substance abuse disorders

Hammett TM, et al. Am J Public Health.
2002921789-1794.
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Why Are Correctional Institutions Important
Targets for Intervention?
HIV-infected persons are frequently diagnosed and
initiate antiretroviral therapy in prison
Other setting 32
Prison 68
Mostashari F, et al. JAIDS. 199818341-348.
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Virologic and Immunologic Outcomes Among
HIV-Infected Recidivists
HIV RNA Change
CD4 Cell Counts
554
1.29
Baseline End of study
P0.018
446
P0.003 P0.013
Change (log10 copies/mL)
CD4 Cell Count (cells/mm3)
224
157
Baseline 2.91
-0.03
Baseline 2.60
Incarcerated Prisoners (n30)
Re-Incarcerated Prisoners (n15)
Incarcerated Prisoners (n30)
Re-Incarcerated Prisoners (n15)
Stephenson BL, et al. Public Health Rep.
20051208488.
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Only the Incarcerated Have a Legal Right to
Healthcare

• The public be required to care for the prisoner
  who cannot by reason of the deprivation of his
  liberty, care for himself.
• Spicer vs Williams 191 NC 1926
• Deliberate indifference to serious medical needs
  of the prisoners is a violation of the 8th
  amendment
• Supreme Court 1976

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Comorbid Conditionsin the Incarcerated Population

• Mental illness
• Substance abuse
• Tuberculosis
• STDs
• Hepatitis, especially HCV
• 1.3 to 1.4 million inmates are HCV
• Prevalence of HCV in inmates 10x that of US
  population
• Incarcerated women have a higher rate of HCV than
  incarcerated men

DeGroot A. HEPP News. April 2001 Baillargeon J,
et al. Public Health. 200311743-48.
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Opportunities for HIV Carein Corrections

• Large reservoir of people living with HIV
• Structured environment with universal access to
  healthcare
• Important site for initiating health promotion
• Improved health in the community post-release
• Decreased transmission of HIV

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Challenges to HIV Carein Corrections

• Lack of HIV specialists, integrated delivery
  systems, community standard practices
• Remote locations
• Continuity of care
• Mistrust and stigma
• Language/cultural barriers
• Restricted formularies
• Confidentiality/privacy

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Considerations for Managementof HIV in
Correctional Settings

• Educating patients about HIV, antiretroviral
  therapy, and adherence
• Initiating treatment
• When to start
• What regimen to use
• Simplicity, dosing, frequency, side effect
  profile, drug interactions
• Planning for continuity of care from the outset

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Antiretroviral Therapyin Correctional Settings
Disadvantages
Advantages

• Structured setting
• Equal access to care
• Availability of ART
• Possible DOT

• Court runs
• Transfers
• Strip searches
• Potential breach of confidentiality
• Unstructured DOT
• ? presence of mental illness

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Selection of Antiretroviral Regimens for the
Incarcerated Patient
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Factors to Consider When Selectingan Initial
Antiretroviral Regimen

• Viral load and CD4 count
• Primary resistance
• Potency
• Adherence potential
• Tolerability/toxicities
• Convenience
• Future options
• Drug interactions
• Comorbidities

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Special Considerations for Initiating ART in
Correctional Settings

• Adequate length of stay to assess initial
  tolerability and response
• Availability of therapy at intake
• Timely renewal of medications
• Organization of medication dispensation
• Adequate discharge medications
• Linkage to community providers

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Considerations in Talking to Your Patients About
Starting ART

• Essential part of the patient-provider
  relationship
• Provide patient with an understanding of possible
  side effects
• Acknowledge that starting ART can be difficult
• Provide a mechanism of support
• Explain the importance of adherence and the
  potential for developing resistance

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WHEN TO START HAART?
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Probability of Survival by CD4 Countand Viral
Load Stratification
Viral Load (copies/mL)
CD4 Cell Count (cells/mm3)
Probability of Survival ()
Probability of Survival ()
Low lt50,000 (n356) Intermediate
gt50,000-199,999 High gt200,000 (n420)
0 6 12 18 24
0 6 12 18 24
Time to Start of ART (Months)
Time to Start of ART (Months)
Hogg RS, et al. JAMA. 20012862568-2577.
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Goals of Therapy and Tools to Achieve Them

• GOALS
• Maximal and durable suppression of viral load.
• Restoration or preservation of immunologic
  function.
• Improvement in quality of life.
• Reduction of HIV-related morbidity and mortality.

• TOOLS
• Maximize adherence to the antiretroviral regimen.
• Rational sequencing of drugs.
• Preservation of future treatment options.
• Use of drug-resistance testing in selected
  clinical
• settings.

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Indications for the Initiation of Antiretroviral
Therapy in the Chronically HIV-Infected Patient
April 2007
Guidelines for the Use of Antiretroviral Agents
in HIV-1-Infected Adults and Adolescents 4/2007
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The Patients First HAART

• Start when the patient (not the provider) is
  emotionally, psychologically and intellectually
  ready to start.
• Explain the natural progression of HIV infection.
• Explain the way the ARVs work against the HIV.
• Know the preferences and concerns of the patient.
• Introduce the adequate ARV regimens according to
  her/his needs.

• HAART IS NOT AN EMERGENCY

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The Doctors First HAAART

• Start with the best regimen for the patient
• Most tolerable.
• Best chance for adherence.
• Most adequate for the patients lifestyle and
  habits.
• The most salvageable.

HAART IS NOT AN EMERGENCY
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THE COMBOSWHAT TO START WITH?
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PRE-HAART RENAL EVALUATION

• Always calculate creatinine clearance when
  considering ART. Use Caukroft-Gault or MDRD
• Renal excretion.
• Serum creatinine IS NOT an accurate marker of
  renal function.
• Adjust the dose of Tenofovir if necessary.
• DO NOT use Truvada or Atripla if Tenofovir
  requires dose adjustment.

Creatinine clearance (140-age)
(Weight-kg) (72) (Serum creatinine-mg/dL) If
female, multiply by 0.85
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Recommended Regimens forTreatment-Naïve
Patients DHHS 2006
Available at www.aidsinfo.nih.gov/guidelines
April 2007.
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Tenofovir Emtricitabine Efavirenz

• Advantages
• One pill QD
• Proven efficacy
• Improves adherence
• Long term safety
• Low incidence of lipoatrophy
• No effect on bone density
• Thoroughly studied

• Disadvantages
• Neuropsychiatric side effects careful in
  psychiatric patients
• Nephrotoxic
• Pregnancy category D
• Hypertriglyceridemia

1 pill
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Zidovudine Lamivudine Efavirenz

• Advantages
• Proven efficacy
• Low pill burden
• Thoroughly studied

• Disadvantages
• BID dosing
• Neuropsychiatric side effects careful in
  psychiatric patients
• Bone marrow suppression anemia, fatigue are
  common side effects
• Pregnancy category D
• Hypertriglyceridemia

3 pills
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Tenofovir Emtricitabine Boosted Atazanavir

• Advantages
• QD
• Proven efficacy
• Improves adherence
• Long term safety
• Low incidence of lipoatrophy
• No effect on bone density
• Safe lipid profile

• Disadvantages
• Hyperbilirubinemia/
• jaundice
• Nephrolithiasis, rare. No hydration requirements.

3 pills
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Zidovudine Lamivudine Boosted Atazanavir

• Advantages
• Proven efficacy
• Safe lipid profile

• Disadvantages
• BID dosing
• Hyperbilirubinemia/
• jaundice
• Nephrolithiasis, rare. No hydration requirements.
• Anemia, fatigue
• Lipoatrophy

4 pills
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Tenofovir Emtricitabine Fosamprenavir
700/Ritonavir 100 BID

• Advantages
• Low pill burden
• Good lipid profile
• Low incidence of long-term toxicities

• Disadvantages
• Nephrotoxicity
• BID dosing
• GI side effects nausea, vomiting, diarrhea

5 pills
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Zidovudine Lamivudine Fosamprenavir
100/Ritonavir 100 BID

• Advantages
• Low pill burden
• Good lipid profile

• Disadvantages
• Anemia, fatigue
• BID dosing
• GI side effects
• Lipoatrophy secondary to ZDV

6 pills
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Tenofovir Emtricitabine Lopinavir /Ritonavir
BID

• Advantages
• Low pill burden
• Proven efficacy in early and advanced disease
• Thoroughly investigated
• Sustained viral suppression in studies over 5
  years

• Disadvantages
• BID dosing
• GI side effects
• Nephrotoxicity
• Hyperlipidemia
• Lipodystrophy

5 pills
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Abacavir Lamivudine

• Advantages
• QD
• Good lipid profile
• Low incidence of GI side effects
• Well tolerated

• Disadvantages
• Close monitoring in patient with hepatic
  impairment
• Hypersensitivity reaction
• Fever, rash, malaise, flu-like symptoms, chest
  pain in 1-6 weeks of initiating treatment
• Test for HLA-B5701

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Case 1

• 32 y/o WM MSM, 2 year sentence, multiple
  disciplinary reports for not following orders.
• HIV infected since 1997, HAART naïve
• No IVDU, no ETOH abuse
• He wants to start ART with the once a day pill.

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Case 1 (cont.)

• Labs
• CBC WBC5,200 Hgb15.2 g/dL Hct40
• Hepatitis Bs Ab (-), HBs Ag (-), HCV Ab (-)
• Creatinine clearance gt60
• CD4300 (25) RNA132,000
• Genotype wild type
• Would you recommend HAART?
• What regimen would you choose?

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Case 2

• 45 y/o AAM, IVDU, promiscous unprotected sex, 10
  year sentence, few DRs.
• HIV infection diagnosed at reception center
• He is unsure of initiating ART due to side
  effects. My friend died on AZT 15 years ago.
• Asymptomatic
• Smoker of 1-2 ppd

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Case 2 (cont.)

• Labs
• CBC WBC3,200 Hgb13.4 g/dL Hct32
• HBsAb (), HBsAg (-), HCV Ab ()
• Creatinine clearancegt60
• CD4220 (18) RNA278, 000
• Lipids Total cholesterol 346 LDL220
• Whats the next step?
• Genotype NRTI K103N PI
  WT
• What regimen would you choose?

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Case 3

• 29 y/o AAF, 3 year sentence for prostitution and
  drug possession, close management
• HIV infected since 2001 when tested for pregnancy
• She was treated with ZDV/3TC during pregnancy and
  stopped after delivery
• No IVDU

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Case 3 (cont.)

• Labs
• CBC WBC4,400 Hgb9.8 g/dL Hct23
• HbsAb (-), HBsAg (), HCV Ab (-)
• AST45 ALT68
• Creatinine clearance gt60
• CD4180 (10) RNA98,000
• Whats the next step?
• Genotype WT
• What regimen would you choose?

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SUMMARY

• Antiretroviral therapy is lifelong treatment
• Should aim to select regimens with
• Good tolerability from the start to ensure
  adherence
• Adequate long-term safety profiles to preserve
  patients quality of life
• ARVs vary in type and degree of toxicities
• We still need to be alert for appearance or
  progression of long-term toxicities
• New ARVs have helped minimize the trade-off
  between efficacy and toxicity

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Thank you!!!