THE CHALLENGE OF THE CHALLENGE OF STARTING HAART IN STARTING HAART IN

CORRECTIONSCORRECTIONS

Ernesto J. Lamadrid, MD, AAHIVS

Florida/Caribbean AETC

August 11, 2007

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.

The Human Immunodeficiency Virus

Adults and children estimated to be living with HIV, 2005

Total: 38.6 (33.4 – 46.0) million

Western & Central Europe

720 000720 000[550 000 – 950 000][550 000 – 950 000]

North Africa & Middle East

440 000440 000[250 000 – 720 000][250 000 – 720 000]Sub-Saharan Africa

24.5 million24.5 million[21.6 – 27.4 million][21.6 – 27.4 million]

Eastern Europe & Central Asia

1.5 million1.5 million [1.0 – 2.3 million][1.0 – 2.3 million]

South & South-East Asia

7.6 million7.6 million[5.1 – 11.7 million][5.1 – 11.7 million]Oceania

78 00078 000[48 000 – 170 000][48 000 – 170 000]

North America1.3 million1.3 million

[770 000 – 2.1 million][770 000 – 2.1 million]

Caribbean330 000330 000

[240 000 – 420 000][240 000 – 420 000]

Latin America1.6 million1.6 million

[1.2 – 2.4 million][1.2 – 2.4 million]

East Asia680 000680 000

[420 000 – 1.1 million][420 000 – 1.1 million]

UNAIDS

Incarceration and HIV/AIDSIncarceration 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. 2002;92:1789-1794.

US HIV Data:Prisons 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 (n=23,046*)

• Males: 1.7% (n=20,668†) • Females: 2.4% (n=2084†)

Maruschak LM. Bur Justice Stat Bull. November 2006.Available at: http://www.ojp.usdoj.gov/bjs/abstract/hivp04.htm.

0

0.5

1

1.5

2

2.5

3HIV Prevalence

Pre

vale

nce

(%

)

All Prisoners(State and Federal)

98 99 00 01 02 03 04

General Population

*Estimated.†Reported. Year

Identified HIV Infection:Distribution by Jurisdiction (2004)

Maruschak LM. Bur Justice Stat Bull. November 2006.Available at: http://www.ojp.usdoj.gov/bjs/abstract/hivp04.htm.

19.5%New York

(n=4500)

14.1%Florida(n=3250)

10.4%Texas(n=2405)

California (n=1212)

Georgia(n=1109)

45.9%45.9%Other State and Federal PrisonsOther State and Federal Prisons

(n=10,570)(n=10,570)

5.3%

4.8%

US AIDS Data:Prisons and General Population

• State and federal prisons (2004)– Overall rate of

confirmed AIDS among the prison population was >3 times that of the general population

• Inmates: 0.5%• General population:

0.15%

Maruschak LM. Bur Justice Stat Bull. November 2006.Available at: http://www.ojp.usdoj.gov/bjs/abstract/hivp04.htm.

0

10

20

30

40

50

60

70Confirmed AIDS Cases

Cas

es p

er 1

0,00

0 All Prisoners(State and Federal)

93 94 95 96 97 98 99 00 01 02 03 04

General Population

Year

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. 2002;92:1789-1794.

Why Are Correctional Institutions Important Targets for Intervention?

HIV-infected persons are frequently diagnosed HIV-infected persons are frequently diagnosed and initiate antiretroviral therapy in prisonand initiate antiretroviral therapy in prison

Prison68%

Other settingOther setting32%32%

Mostashari F, et al. JAIDS. 1998;18:341-348.

Virologic and Immunologic Outcomes Among HIV-Infected Recidivists

-0.5

-0.3

-0.1

0.1

0.3

0.5

0.7

0.9

1.1

1.3

1.5

Ch

ang

e (l

og

10 c

op

ies/

mL

)

-0.03

HIV RNA Change

Stephenson BL, et al. Public Health Rep. 2005;120:84:88.

+1.29*

IncarceratedPrisoners

(n=30)

Re-IncarceratedPrisoners

(n=15)

0

100

200

300

400

500

600

CD

4 C

ell C

ou

nt

(cel

ls/m

m3 )

446

CD4 Cell Counts

224

IncarceratedPrisoners

(n=30)

Re-IncarceratedPrisoners

(n=15)

Baseline2.60

Baseline2.91

554*

157†

BaselineEnd of study

*P=0.003†P=0.013

*P=0.018

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

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 menDeGroot A. HEPP News. April 2001; Baillargeon J, et al. Public Health. 2003;117:43-48.

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

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

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

Antiretroviral Therapyin Correctional Settings

• 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

AdvantagesAdvantages DisadvantagesDisadvantages

Selection of Antiretroviral Regimens for the Incarcerated

Patient

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

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

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

Probability of Survival by CD4 Countand Viral Load Stratification

Viral Load (copies/mL)Viral Load (copies/mL)

Hogg RS, et al. JAMA. 2001;286:2568-2577.

0

20

40

60

80

100

0 6 12 18 240 6 12 18 24

Pro

bab

ility

of

Su

rviv

al (

%)

Pro

bab

ility

of

Su

rviv

al (

%)

CD4 Cell Count (cells/mmCD4 Cell Count (cells/mm33))

Time to Start of ART (Months)

Low: <50 (n=142)Low: <50 (n=142)Intermediate: Intermediate: >>50-199 (n=301)50-199 (n=301)High High >>200 (n=776)200 (n=776)

0

20

40

60

80

100

0 6 12 18 0 6 12 18 2424

Pro

bab

ility

of

Su

rviv

al (

%)

Pro

bab

ility

of

Su

rviv

al (

%)

Time to Start of ART (Months)

Low: <50,000 (n=356)Low: <50,000 (n=356)Intermediate: Intermediate: >>50,000-199,99950,000-199,999High High >>200,000 (n=420)200,000 (n=420)

Goals of Therapy and Tools to Achieve Goals of Therapy and Tools to Achieve ThemThem

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.

Indications for the Initiation of Antiretroviral Therapy in the Chronically HIV-Infected

Patient: April 2007Clinical Category CD4 Cell Count Plasma HIV RNA Recommendation

Symptomatic Any value Any value Treat

Asymptomatic, AIDS

CD4<200 cells/mm3

Any value Treat

Asymptomatic CD4 >200 but <350 cells/mm3

Any value Treatment should generally be offered, but controversy exists.

Asymptomatic CD4 > 350 cells/mm3

>100,000 copies/mL

Some experts recommend initiating therapy.

Asymptomatic CD4 > 350 <100,000 copies/mL

Many experts defer therapy and observe.

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents 4/2007

The Patient’s First HAARTThe Patient’s 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 ARV’s 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 EMERGENCYHAART IS NOT AN EMERGENCY

The Doctor’s First HAAARTThe Doctor’s First HAAART

Start with the best regimen for the patient:

Most tolerable.

Best chance for adherence.

Most adequate for the patient’s lifestyle and habits.

The most salvageable.

HAART IS NOT AN EMERGENCYHAART IS NOT AN EMERGENCY

THE COMBO’S:WHAT TO START WITH?

PRE-HAART RENAL PRE-HAART RENAL EVALUATIONEVALUATION

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

Recommended Regimens forTreatment-Naïve Patients: DHHS 2006

Available at: www.aidsinfo.nih.gov/guidelines April 2007.

Column A Column B

NNRTI PI NRTI

Preferred(alphabetical order)

Efavirenz Atazanavir + Ritonavir

Fosamprenavir+

Ritonavir BID

Lopinavir+Ritonavir BID

Tenofovir/

emtricitabine

Zidovudine/

lamivudine

Alternative(alphabetical order)

Nevirapine Atazanavir unboosted

Fosamprenavir unboosted

Fosamprenavir+

Ritonavir QD

Lopinavir+Ritonavir QD

Abacavir/

lamivudine

Didanosine/ lamivudine

Tenofovir + Emtricitabine + Efavirenz

AdvantagesOne pill QD

Proven efficacy

Improves adherence

Long term safety

Low incidence of lipoatrophy

No effect on bone density

Thoroughly studied

DisadvantagesNeuropsychiatric side effects: careful in psychiatric patients

Nephrotoxic

Pregnancy category D

Hypertriglyceridemia

1 pill

Zidovudine + Lamivudine + Efavirenz

AdvantagesProven efficacy

Low pill burden

Thoroughly studied

DisadvantagesBID dosingNeuropsychiatric side effects: careful in psychiatric patientsBone marrow suppression: anemia, fatigue are common side effectsPregnancy category DHypertriglyceridemia

3 pills

Tenofovir + Emtricitabine + Boosted Atazanavir

AdvantagesQDProven efficacyImproves adherenceLong term safetyLow incidence of lipoatrophyNo effect on bone densitySafe lipid profile

DisadvantagesHyperbilirubinemia/

jaundiceNephrolithiasis, rare. No hydration requirements.

3 pills

Zidovudine + Lamivudine + Boosted Atazanavir

AdvantagesProven efficacy

Safe lipid profile

DisadvantagesBID dosingHyperbilirubinemia/

jaundiceNephrolithiasis, rare. No hydration requirements.Anemia, fatigueLipoatrophy

4 pills

Tenofovir +Emtricitabine + Fosamprenavir 700/Ritonavir 100 BID

AdvantagesLow pill burden

Good lipid profile

Low incidence of long-term toxicities

DisadvantagesNephrotoxicity

BID dosing

GI side effects: nausea, vomiting, diarrhea

5 pills

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 ZDV6 pills

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

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-B*5701

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”.

Case #1 (cont.)

Labs:CBC: WBC=5,200 Hgb=15.2 g/dL Hct=40%Hepatitis Bs Ab (-), HBs Ag (-), HCV Ab (-)Creatinine clearance >60CD4=300 (25%) RNA=132,000Genotype: wild type

Would you recommend HAART?

What regimen would you choose?

Case #2

• 45 y/o AAM, IVDU, promiscous unprotected sex, 10 year sentence, few DR’s.

• 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

Case #2 (cont.)

Labs:CBC: WBC=3,200 Hgb=13.4 g/dL Hct=32%HBsAb (+), HBsAg (-), HCV Ab (+)Creatinine clearance>60CD4=220 (18%) RNA=278, 000 Lipids: Total cholesterol 346 LDL=220

What’s the next step?

Genotype: NRTI: K103N PI: WT

What regimen would you choose?

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

Case #3 (cont.)

Labs:CBC: WBC=4,400 Hgb=9.8 g/dL Hct=23%HbsAb (-), HBsAg (+), HCV Ab (-)AST=45 ALT=68Creatinine clearance >60CD4=180 (10%) RNA=98,000

What’s the next step?

Genotype: WT

What regimen would you choose?

SUMMARYSUMMARY

• 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