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HIV Treatment and Guideline Update 2010

HIV Treatment and Guideline Update 2010. Aaron Huwe, Pharm.D. Senior Medical Scientist - Managed Markets Gilead Sciences, Inc. May 19 th , 2010. Disclosures. Employee of Gilead Sciences Affiliated with UCSF School of Pharmacy

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HIV Treatment and Guideline Update 2010

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  1. HIV Treatment and Guideline Update 2010 Aaron Huwe, Pharm.D. Senior Medical Scientist - Managed Markets Gilead Sciences, Inc. May 19th, 2010

  2. Disclosures • Employee of Gilead Sciences • Affiliated with UCSF School of Pharmacy • Pharmacist first and foremost and will provide a fair-balanced discussion

  3. Introduction • Section One: HIV Disease Overview • Section Two: HIV Testing/Screening • Section Three: Benefits of HIV Therapy • Section Four: HIV Treatment Guidelines • Section Five: HIV Adherence and Persistency

  4. Section One:HIV Disease Overview

  5. HIV Disease Function • HIV primarily infects vital cells of the human immune system • Helper T cells (CD4) • HIV depletes CD4+ T lymphocytes three ways: • Viral killing of infected cells • Increased rates of apoptosis in infected cells • Killing by CD8 cytotoxic lymphocytes Hoffman, C., Rockstroh, J.K., Kamps, B.S. HIV Medicine 2007, 15th edition, www.hivmedicine.com, accessed January 4, 2008

  6. HIV Life Cycle and Treatment Targets CCR5 Inhibitors Non-Nucleoside & Nucleoside Reverse Transcriptase Inhibitors Integrase Inhibitors Protease Inhibitors HIV virion New HIV particle Capsid proteins CD4 Host receptor chromosome Viral mRNA cDNA Glycoprotein RER Proviral DNA Genomic RNA Unintegrated ds DNA Genomic RNA Nucleus Attachment Assembly & Release Uncoating Translation & Processing Reverse Transcription Integration Transcription

  7. HIV disease is diagnosed by a blood test for antibodies or an HIV Viral Load An AIDS diagnosis requires: Less than 200 CD4+ T-lymphocytes/uL or a CD4+ T-lymphocyte percentage of total lymphocytes of less than 14% And/or one opportunistic infection or malignancy. Clinical Definition of HIV / AIDS Hoffman, C., Rockstroh, J.K., Kamps, B.S. HIV Medicine 2007, 15th edition, www.hivmedicine.com, accessed January 4, 2008

  8. Goal of HIV Treatment Achieving a stable or rising T-cell count and an undetectable viral load Viral Load (undetectable) T-cell Count (stable or rising)

  9. Typical Course of Untreated HIV Infection Viral Load CD4 Pantaleo G. Virologic and immunologic events associated with primary HIV infection, pp. 655-7. In: Fauci AS, moderator. Immunopathogenic mechanisms of HIV infection. Ann Intern Med. 1996:124:654-63.

  10. Main Transmission Routes • Sexual Route • The majority of HIV infections are acquired through unprotected sexual relations. Sexual transmission can occur when infected sexual secretions of one partner come into contact with the genital, oral, or rectal mucus membranes of another. • Blood or blood product route • Injection drug users (IDU), sharing of needles • Hemophiliacs • Recipients of transfusions • Tattoo, piercing, scarification procedures • Occupational • Mother to child • Pregnancy/Birth • Breast Feeding The potential risk of infection from saliva, tears and urine is negligible, as HIV in these body fluids is found in low concentrations of infected individuals. http://www.niaid.nih.gov/factsheets/hivinf.htm, accessed January 4, 2008

  11. Eastern Europe & Central Asia 1.6 million [1.2 – 2.1 million] Western & Central Europe 760 000 [600 000 – 1.1 million] North America 1.3 million [480 000 – 1.9 million] East Asia 800 000 [620 000 – 960 000] North Africa & Middle East 380 000 [270 000 – 500 000] Caribbean 230 000 [210 000 – 270 000] South & Southeast Asia 4 million [3.3 – 5.1 million] Sub-Saharan Africa 22.5 million [20.9 – 24.3million] Latin America 1.6 million [1.4 – 1.9 million] Oceania 75 000 [53 000 – 120 000] Total: 33.2 (30.6 – 36.1) million Estimates of Adults and Children Living With HIV at the End of 2007 Joint United Nations Programme on HIV/AIDS (UNAIDS) and World Health Organization (WHO) 2007.

  12. Eastern Europe & Central Asia 150 000 [70 000 – 290 000] Western & Central Europe 31 000 [19 000 – 86 000] North America 46 000 [38 000 – 68 000] East Asia 92 000 [21 000 – 220 000] North Africa & Middle East 35 000 [16 000 – 65 000] Caribbean 17 000 [15 000 – 23 000] South & Southeast Asia 340 000 [180 000 – 740 000] Sub-Saharan Africa 1.7 million [1.4 – 2.4 million] Latin America 100 000 [47 000 – 220 000] Oceania 1400 [1100 – 26 000] Estimates of New HIV Infection in Adults and Children at the End of 2007 Total: 2.5 (1.8 – 4.1) million Joint United Nations Programme on HIV/AIDS (UNAIDS) and World Health Organization (WHO) 2007.

  13. Estimated Number of AIDS Cases and Deaths Among US Adults and Adolescents 450 400 350 300 250 200 150 100 50 0 AIDS Prevalence AIDS Cases Number of AIDS Cases and Deaths (x1000) Prevalence (x1000) AIDS Deaths 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.

  14. ~79% ~83% ~75% U.S. HIV Landscape 1,056 – 1,156 835 – 915 675 560 Sources: * February, 2009 CDC estimates as of the end of 2006 ** Synovate Healthcare U.S. HIV Monitor Q3 2008

  15. CDC: Estimated HIV Prevalencein the United States • Estimated HIV prevalence (2006) • 1.1 million adults and adolescents Estimated Prevalence of HIV Infection in US 2006 21% 79% “Effective testing programs, along with early access to treatment and prevention services, are integral for reducing undiagnosed HIV infections.” HRHC: high-risk heterosexual contact. Campsmith M, et al. MMWR. October 3, 2008; 57(39):1073-1076.

  16. Proportion of HIV/AIDS Cases and Population by Race/Ethnicity, 2005 33 States Note: Data includes persons diagnosed with HIV infection regardless of their AIDS status at diagnosis. Data from 33 states with name-based confidential HIV infection reporting since at least 2001. Data have been adjusted for reporting delays. * Data includes 257 persons of unknown or multiple races. Centers for Disease Control and Prevention, 2005 MMWR HIV/AIDS Report

  17. WA WA WA NH NH NH ME ME ME MT MT MT VT VT VT ND ND ND MN MN OR MN OR OR MA MA MA ID ID ID AIDS Prevalence Hispanic AIDS Prevalence Black AIDS Prevalence WI WI WI NY NY NY NY NY NY SD SD SD RI RI RI WY WY WY MI MI MI CT CT CT CT IO IO IO PA PA PA PA PA PA NJ NJ NJ NJ NJ NE NJ NE NE NV NV NV FL FL FL DE DE DE FL FL FL IL IL IL UT UT UT CO CO CO WV WV WV CA CA CA MD MD MD MD VA VA VA KS KS VA VA KS MO MO MO MO KY KY KY DC DC DC AK AK AK NC NC NC TN TN TN TN TN OK OK OK AZ AZ AZ AZ NM SC NM SC NM SC AR AR AR MS MS AL AL GA GA GA MS AL GA GA LA LA LA LA LA TX TX TX TX TX TX FL FL FL FL FL FL HI HI HI “The Top 10”

  18. Section Two:The Importance of HIV Screening

  19. Importance of Screening for HIV Disease Introduction • Early HIV screening and linkage to care • reduces the frequency of hospitalizations • reduces overall cost of care • Early treatment • reduces transmission potential • potential increase of lifespan

  20. Accounting for: ~54% of New Infections ~75% Aware of Infection ~46% of New Infections New Sexual Infections Each Year: ~32,000 People Living with HIV/AIDS: 1,039,000-1,185,000 Awareness of Serostatus AmongPeople with HIV: Estimates of Transmission ~25% Unaware of Infection Marks, G., Crepaz, N., Janssen, R.S., Estimating sexual transmission of HIV from persons aware and unaware that they are infected with the virus in the USA, AIDS 2006, 20:1447-50.

  21. Estimated Number of AIDS Cases and Deaths Among US Adults and Adolescents 450 400 350 300 250 200 150 100 50 0 AIDS Prevalence AIDS Cases Number of AIDS Cases and Deaths (x1000) Prevalence (x1000) AIDS Deaths 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.

  22. 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 • Resulting in increases in HIV testing rates • Pretest counseling not required • Repeat HIV testing left to discretion of provider, based on risk • State Testing Laws: • 15 states have updated laws since CDC issued revised recommendations (Arizona, California, Connecticut, Hawaii, New Hampshire, New Mexico, North Carolina, Maine, Maryland, Montana, Louisiana, Iowa, Illinois, Indiana, Virginia) • 8 states still requiring written informed consent = Alabama, Massachusetts, Michigan, Nebraska, New York, Pennsylvania, Rhode Island, Wisconsin Branson BM, et al. MMWR Recomm Rep. 2006;55(RR-14):1-17.

  23. Implies all patients are considered candidates for screening Testing is part of standard panel of tests All patients are offered the option to decline the test. The test is performed unless the patient specifically refuses Requires providers to specifically recommend HIV testing and for patients to specifically agree to testing May assume that clinicians assess which patient is at-risk for infection Greater reluctance on part of patient Requires more staff time Opt-Out Versus Opt-In Screening Opt-Out Screening Opt-In Screening Branson BM, et al. MMWR Recomm Rep. 2006;55(RR-14):1-17.

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

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

  26. Where People Get Tested 1 National Health Interview Survey, 2006 2 Supplemental to HIV/AIDS Surveillance, 2000-2003. CDC

  27. HIV Screening by Potential AIDS Defining Event in a Privately Insured US Population Review of 8 US Health Plans - 7,451 patients • 4.3% Patients Screened for HIV with Any Potential AIDS Defining Event • 12.5% Patients Screened for HIV with Multiple Potential AIDS Defining Events Chen JY, CROI 2009; 1044

  28. “Late Testers” Account forApproximately 40% of HIV Diagnoses Males Females Early tester Late tester Early tester Late tester 65% 63% 60% 59% 54% 53% 53% 50% 47% 47% 46% 41% 40% HIV Diagnosis (%) HIV Diagnosis (%) 37% 35% MSM IDU MSM + IDU Hetero- sexual IDU Hetero- sexual Other Other CDC. HIV/AIDS Surveillance Report. June 2007;17. Revised Edition.

  29. National HIV Behavioral Surveillance: Unrecognized HIV Infection • Cross-sectional study • 5-city data collection system • Baltimore, Los Angeles, Miami, New York City, and San Francisco • Men who have sex with men • 83% participation rate • Participants tested for HIV infection • Surveyed about knowledge of their HIV status Unrecognized Infection 79% 70% 49% Prevalence (%) 34% 30% 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.

  30. Provider Barriers to HIV Testing:Prenatal, EDs and Other Medical Settings Burke RC, et al. AIDS 2007, vol. 21, no12, pp. 1617-1624

  31. DC Emergency Patients Who Decline HIV Test Have Twice Higher HIV Rate Reasons for Declining 48, 128 Patients Evaluated 7558 Individuals Offered Testing 4845 Accepted Testing 2713 Declined Testing 35 Preliminary Positive 600 Samples Collected Not at risk Recently tested (4+ months ago) Declined to give a reason Unknown/Not Reported Afraid to find out Patient would rather test elsewhere 12 Preliminary Positive 0.7% Seropositivity 2% Seropositivity Czamogorski, et al., ICAAC 2009; Poster #H-239.

  32. HIV Testing Best Practices

  33. Recommendations for Pregnant Women CDC Recommendations1 • Universal opt-out screening as routine panel of prenatal screening tests • Second test in third trimester for women who are known to be at risk for HIV • Labor & delivery opt-out 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 ARV prophylaxis within 12 hours of birth on basis of rapid test result ACOG Recommendations2 • Recommends opt-out HIV screening for women aged 19 to 64 years • Targeted screening for women with risk factors outside this age range • Annually review patient’s risk factors for HIV for potential re-testing • Repeat HIV testing should be offered annually for women in high risk groups • Encourage women to be tested before initiating a new sexual relationship, • Branson BM, et al. MMWR Recomm Rep. 2006;55(RR-14):1-17. • ACOG Committee Opinion Number 411. Obstet Gynecol. 2008;114:401-403

  34. Prevention Success:Perinatally Acquired AIDS Cases 1985-2006 PACTG 076 (AZT Significantly  MTCT) CDC HIV Screening Recs Number of AIDS Cases ~95% Reduction 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 Year of Diagnosis or Death CDC. HIV/AIDS Surveillance Report, 2006. 2008;18:1-55. Available at:http://www.cdc.gov/hiv/topics/surveillance/resources/reports/.

  35. Washington DC HIV Routine Opt-out Testing Expansion • Encouraged “opt out” HIV testing in medical settings • Increased jail testing, school testing, needle exchange, and couples services • Resulted in 1 year increase in testing from 43,271 tests to 72,864 tests 12.7% 68.4% increase in number of tests done 18.2% 87.3% 81.8% N=72,864 N=43,721 Hader, S, 16th CROI 2009; 57

  36. Median CD4 Count at Time of Testing 350 332 300 262 250 220 215 198 187 200 183 Median CD4 Count 150 100 50 0 2001 2002 2003 2004 2005 2006 2007 Year of HIV Diagnosis Washington DC HIV Testing Expansion:Earlier Diagnosis Helps Identify HIV+ People at Higher CD4+ Counts • Testing in EDs, hospitals, STD clinics • Expanded HIV testing in jails, schools, needle exchange, and couples services • Encouraged “opt out” HIV testing in medical settings • Through these efforts they were able to increase the number of tests given from • 43,271 tests done in 2007 • 72,864 tests done in 2008 • 68.4% increase • In addition, they were able to find patients with higher CD4 counts at initial testing • 2004 – 198 cells/mm3 • 2007 – 332 cells/mm3 Hader, S, 16th CROI 2009; 57

  37. Change in Policy has Significant Impact:San Francisco Department of Public Health Medical Care System Requirement for written consent for HIV testing eliminated Tests per 1,000 Visits 30.6 HIV positive tests per month 20.6 HIV positive tests per month Mean rate of HIV tests per 1,000 patient-visits in persons aged 18 years or older (Dec ’03 – Dec ’06), Zetola et al, JAMA March, 2007.

  38. Section Three:Impact of HIV Treatment

  39. HIV Life Cycle and Treatment Targets CCR5 Inhibitors Non-Nucleoside & Nucleoside Reverse Transcriptase Inhibitors Integrase Inhibitors Protease Inhibitors HIV virion New HIV particle Capsid proteins CD4 Host receptor chromosome Viral mRNA cDNA Glycoprotein RER Proviral DNA Genomic RNA Unintegrated ds DNA Genomic RNA Nucleus Attachment Assembly & Release Uncoating Translation & Processing Reverse Transcription Integration Transcription

  40. Approved Antiretrovirals Between ’87 and ’95, 4 antiretrovials were launched. Since ’95, 28 new products were introduced. Videx EC Atripla Hivid Viread Rescriptor Truvada Trizivir Isentress Viramune Epzicom Ziagen Combivir Epivir Sustiva Intelence Zerit Emtriva Retrovir Videx 1987 ’88 ’89 ’90 ’91 ’92 ’93 ’94 ’95 ’96 ’97 ’98 ’99 ’00 ’01 ’02 ’03 ’04 ’05 ’06 ’07 ‘08 NRT-I Aptivus Invirase Kaletra Viracept Protease-I Norvir Prezista Reyataz Agenerase NNRT-I Crixivan Lexiva Selzentry Fusion-I Fortovase Fuzeon CCR5-I Integrase-I http://www.fda.gov/oashi/aids/virals.html

  41. Impact of HIV Treatment on Lifespan • 2.8 million years of life saved • 1.2 million years already lived • 1.6 million years life years remain • Only applies to those in care, including prophylactic and antiretroviral therapies combined • Economic impact of treatment is highly significant Walensky, RP, Paltiel, A.D., Losina, E., Mercincavage, L.M., et.al., The survival benefit of AIDS treatment in the United States, Journal of Infectious Diseases, 2006: 194 (July) 11-19.

  42. pMTCT = prevention of mother-to-child transmission ART 1 = (1996-97) protease inhibitor (PI)-based treatment ART 2 = (1998-99) sequential NNRTI-based regimens followed by PI-based regimens ART 3 = (2000-02) 3 effective regimens with increased options for salvage through resistance testing and boosted PI therapy ART 4 = (2003) improved drug efficacy/tolerability and decreased complexity – introduction of fusion inhibitors. Evolution of HIV Treatment Walensky, RP, Paltiel, A.D., Losina, E., Mercincavage, L.M., et.al., The survival benefit of AIDS treatment in the United States, Journal of Infectious Diseases, 2006: 194 (July) 11-19.

  43. HIV Treatment Impact on Lifespan Walensky, RP, Paltiel, A.D., Losina, E., Mercincavage, L.M., et.al., The survival benefit of AIDS treatment in the United States, Journal of Infectious Diseases, 2006: 194 (July) 11-19.

  44. Comparative Survival Gains from Treatment 160 Figures shown in months, 2004 data. 92 50 3 29 7 7 29 50 92 3 160 Intervention Chemotherapy Adjuvant Comprehensive Bone Marrow Opportunistic Antiretroviral Chemotherapy post-MI care Transplant Infection Therapy Prophylaxis Disease Non-small-cell Node+ breast Coronary artery Relapsed non- AIDS lung cancer cancer disease Hodgkins lymphoma Walensky, RP, Paltiel, A.D., Losina, E., Mercincavage, L.M., et.al., The survival benefit of AIDS treatment in the United States, Journal of Infectious Diseases, 2006: 194 (July) 11-19.

  45. Trends in AIDS-Related Deaths and Antiretroviral Availability AIDS-Related Deaths 50,877 Number 18,017 14,546 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 NRTIsZDV ddI ddC d4T 3TC * ABC † TDF FTC §¶ SQV RTV NFV APV LPV/r FPV TPV IDV ATV DRV PIs NNRTIsNVP DLV EFV OtherENF II/ CCR5 *Zidovudine/lamivudine; †zidovudine/lamivudine/abacavir; §emtricitabine/tenofovir DF; ¶abacavir/lamivudine. CDC: Surveillance Report. 2003.

  46. Effective HAART Reduces Hospitalizations • Study compared hospital admissions in 6 states in 2000 and in 2004 • California, Florida, New Jersey, New York, South Carolina, and Washington • The study found a 20% reduction in Hospital Admissions between 2000 and 2004 with the advancing access to effective combination Antiretroviral Therapy • The study found a 38% reduction in Hospital Costs Per Person between 2000 and 2004 Hellinger, F. J., PhD, The changing pattern of hospital care for persons living with HIV, Epidemiology and Social Science, Volume 45, Number 2, June 1, 2007

  47. Effective HAART Reduces Hospitalizations Per 100 Patients Average annual number of hospital admissions per 100 patients living with HIV Hellinger, F. J., PhD, The changing pattern of hospital care for persons living with HIV, Epidemiology and Social Science, Volume 45, Number 2, June 1, 2007

  48. High Cost of Medical Care for PatientsWho Present Late (CD4<200 cells/mL) with HIV Krentz, HB; Auld, MC; Gill, MJ:,The high cost of medical care for patients who present late (CD4<200 cells) with HIV Infection, HIV Medicine (2004, 5, 93-98), British HIV Association.

  49. Treatment of patients with CD4 ≥ 3501 Reduces death and progression to AIDS Increases CD4 counts and decreases viral load Preserves immune function Treatment initiation of patients with CD4 ≥ 2001 decreases incidence in peripheral neuropathy, anemia, and renal insufficiency HAART provides economic benefits2 Serves to principally drive CD4 cell count improvement Decreases long-term expenses due to cost avoidance such as hospitalization Cost Benefit of Early Screening & Treatment 1Lichtenstein, K.A., Armon, C., Buchacz, K., Chmiel, J.S., et al, Initiation of antiretroviral therapy…, Journal of Acquired Immune Deficiency Syndrome, Volume 47, Number 1, January 1, 2008 2 Chen, R.Y., Accortt, N.A., Westfall, A.O., Mugavero, M.J., Raper, J.L. et al, Distribution of Health Care Expenditures for HIV Infected Patients, Clinical Infectious Diseases, 2006; 42, 1 April, 1003-1010.

  50. Obstacles to Successful Antiretroviral Therapy • Drug Resistance • DHHS guidelines stress genotypic drug testing for all treatment-naïve patients entering care, regardless of therapeutic start • Adherence • The necessity for patient adherence to a long-term drug regimen should be discussed in depth by the patient and clinician. • Barriers to adherence should be addressed before therapy is initiated. • Long-term toxicity • Mitochondrial toxicity • Lipid disorders • Body composition abnormalities known as lipodystrophy DHHS guidelines 1/2008 http://aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?MenuItem=Guidelines&Search=Off&GuidelineID=7&ClassID=1, site accessed January 4, 2008

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