THE CHALLENGE OF STARTING HAART IN CORRECTIONS

THE CHALLENGE OF STARTING HAART IN CORRECTIONS 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 Western & Eastern Europe Central Europe & Central Asia North America [770 000 – 2.1 million] 1.3 million [550 000 – 950 000] 720 000 [1.0 – 2.3 million] East Asia [420 000 – 1.1 million] 1.5 million Caribbean [240 000 – 420 000] 330 000 North Africa & Middle East [250 000 – 720 000] 680 000 440 000 South & South-East Asia Sub-Saharan Africa Latin America [1.2 – 2.4 million] 1.6 million [21.6 – 27.4 million] 24.5 million 7.6 million [5.1 – 11.7 million] Oceania [48 000 – 170 000] 78 000 UNAIDS Total: 38.6 (33.4 – 46.0) million 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. 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*) *Estimated. †Reported. 3 2.5 HIV Prevalence Prevalence (%) 2 All Prisoners (State and Federal) 1.5 1 0.5 0 • Males: 1.7% (n=20,668†) • Females: 2.4% (n=2084†) General Population 98 99 00 Year 01 02 03 04 Maruschak LM. Bur Justice Stat Bull. November 2006. Available at: http://www.ojp.usdoj.gov/bjs/abstract/hivp04.htm. Identified HIV Infection: Distribution by Jurisdiction (2004) 14.1% Florida 19.5% New York (n=4500) (n=3250) 10.4% Texas (n=2405) California 5.3% (n=1212) 4.8% Georgia (n=1109) 45.9% Other State and Federal Prisons (n=10,570) Maruschak LM. Bur Justice Stat Bull. November 2006. Available at: http://www.ojp.usdoj.gov/bjs/abstract/hivp04.htm. 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% Cases per 10,000 70 60 50 40 30 20 10 0 Confirmed AIDS Cases All Prisoners (State and Federal) 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/abstract/hivp04.htm. Why Care About the Health of 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 and initiate antiretroviral therapy in prison Other setting 32% Prison 68% Mostashari F, et al. JAIDS. 1998;18:341-348. Virologic and Immunologic Outcomes Among HIV-Infected Recidivists 1.5 HIV RNA Change *P=0.018 600 CD4 Cell Counts 554* 446 Baseline End of study Change (log10 copies/mL) CD4 Cell Count (cells/mm3) 1.3 1.1 0.9 0.7 0.5 0.3 0.1 +1.29* 500 400 300 *P=0.003 †P=0.013 224 200 100 0 157† -0.1 -0.3 -0.5 -0.03 Baseline 2.60 Baseline 2.91 Incarcerated Prisoners (n=30) Re-Incarcerated Prisoners (n=15) Incarcerated Prisoners (n=30) Re-Incarcerated Prisoners (n=15) Stephenson BL, et al. Public Health Rep. 2005;120:84:88. 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 Conditions in 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. 2003;117:43-48. Opportunities for HIV Care in 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 postrelease • Decreased transmission of HIV Challenges to HIV Care in 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 Management of 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 Therapy in Correctional Settings • • • • Advantages Structured setting Equal access to care Availability of ART Possible DOT Disadvantages • • • • Court runs Transfers Strip searches Potential breach of confidentiality • “Unstructured” DOT •  presence of mental illness Selection of Antiretroviral Regimens for the Incarcerated Patient Factors to Consider When Selecting an 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 Count and Viral Load Stratification CD4 Cell Count (cells/mm3) 100 Viral Load (copies/mL) Probability of Survival (%) 100 Probability of Survival (%) 80 80 60 60 40 40 20 Low: <50 (n=142) Intermediate: >50-199 (n=301) High >200 (n=776) 20 Low: <50,000 (n=356) Intermediate: >50,000-199,999 High >200,000 (n=420) 0 0 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. 2001;286:2568-2577. 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. Indications for the Initiation of Antiretroviral Therapy in the Chronically HIV-Infected Patient: April 2007 Clinical Category CD4 Cell Count Plasma HIV RNA Recommendation Symptomatic Asymptomatic, AIDS Asymptomatic Any value CD4<200 cells/mm3 CD4 >200 but <350 cells/mm3 Any value Any value Any value Treat Treat Treatment should generally be offered, but controversy exists. Some experts recommend initiating therapy. Many experts defer therapy and observe. Asymptomatic CD4 > 350 cells/mm3 CD4 > 350 >100,000 copies/mL <100,000 copies/mL Asymptomatic Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents 4/2007 The 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 EMERGENCY The 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 EMERGENCY THE COMBO’S: WHAT TO START WITH? 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 creatininemg/dL) If female, multiply by 0.85 Recommended Regimens for Treatment-Naïve Patients: DHHS 2006 Column A NNRTI PI Column B NRTI Tenofovir/ emtricitabine Zidovudine/ lamivudine Abacavir/ lamivudine Didanosine/ lamivudine Preferred (alphabetical order) Efavirenz Atazanavir + Ritonavir Fosamprenavir+ Ritonavir BID Lopinavir+Ritonavir BID Atazanavir unboosted Fosamprenavir unboosted Fosamprenavir+ Ritonavir QD Lopinavir+Ritonavir QD Alternative (alphabetical order) Nevirapine Available at: www.aidsinfo.nih.gov/guidelines April 2007. 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 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 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 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 Tenofovir +Emtricitabine + Fosamprenavir 700/Ritonavir 100 BID Advantages Low pill burden Good lipid profile Low incidence of longterm toxicities Disadvantages Nephrotoxicity BID dosing GI side effects: nausea, vomiting, diarrhea 5 pills Zidovudine + Lamivudine + Fosamprenavir 100/Ritonavir 100 BID Advantages • Low pill burden • Good lipid profile • • • • 6 pills Disadvantages Anemia, fatigue BID dosing GI side effects Lipoatrophy secondary to ZDV 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, flulike 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 >60  CD4=300 (25%) RNA=132,000  Genotype: 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>60  CD4=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=68  Creatinine clearance >60  CD4=180 (10%) RNA=98,000 What’s the next step? Genotype: WT What regimen would you choose? 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 tradeoff between efficacy and toxicity