NORTHWEST AIDS EDUCATION AND TRAINING CENTER HIV Update 2015 Lara Strick, MD, MS Infectious Disease Physician, WA DOC Corrections Program Director, Northwest AETC Clinical Assistant Professor, University of Washington NO CONFLICTS OF INTEREST TO DISCLOSE WA Corrections Conference 3/28/2015
Topics New Testing Algorithm New Medications Antiretroviral Therapy Guidelines Importance of Adherence Patient Barriers to Adherence Monitoring Adherence
New CDC HIV Diagnostic Testing Algorithm
Traditional Approach to HIV Diagnostic Testing Initial EIA Repeatedly Reactive Supplemental Western blot or IFA Optimized for Sensitivity Optimized for Specificity EIA = Enzyme immunoassay IFA = Immunofluorescence assay Source: CDC and Prevention. MMWR Recomm Rep. 2001;50(RR-19):1-57.
Traditional Approach to HIV Diagnostic Testing Initial EIA Repeatedly Reactive Supplemental Western blot or IFA Optimized for Sensitivity Optimized for Specificity Insensitive in acute infection Complex test to run Results not timely Doesn t differentiate HIV-1 & HIV-2 Source: CDC and Prevention. MMWR Recomm Rep. 2001;50(RR-19):1-57.
Early HIV Infection and Test Reactivity HIV RNA p24 Ag EIA (3 rd Gen) Rapid WB 0 5 10 15 20 25 30 35 40 45 50 Days following HIV Acquisition
2014 CDC Draft Recommendations Diagnostic Laboratory Testing for HIV infection in the U.S. Source: Branson B. CDC and Prevention.
2014 CDC Recommendations Diagnostic Laboratory Testing for HIV infection in the U.S. 4 th Generation HIV-1/2 Ag/Ab Immunoassay Source: Branson B. CDC and Prevention.
HIV Capsid (p24 antigen) HIV core Source: David Spach, MD
4 th Generation HIV Ag/Ab Combo ARCHITECT HIV Ag/Ab Combo Chemiluminescent Immunoassay (Abbott Laboratories) GS HIV Combo Ag/Ab Enzyme Immunoassay (Bio-Rad Laboratories) HIV p24 Antigen HIV Antibodies Combo assays detect HIV-1 p24 antigen and antibodies to HIV-1 and HIV-2 Reduces window by about 10-15 days Detects approximately 80% of persons with acute HIV
2014 CDC Recommendations Diagnostic Laboratory Testing for HIV infection in the U.S. 4 th Generation HIV-1/2 Ag/Ab Immunoassay (+) (-) Source: Branson B. CDC and Prevention.
2014 CDC Recommendations Diagnostic Laboratory Testing for HIV infection in the U.S. 4 th Generation HIV-1/2 Ag/Ab Immunoassay (+) (-) Negative for HIV-1 and HIV-2 antibodies and p24 Ag HIV-1/HIV-2 Ab Differentiation Assay Source: Branson B. CDC and Prevention.
FDA-approved HIV-1/HIV-2 Differentiation Immunoassay Multispot HIV-1/HIV-2 Rapid Test Procedural Control Recombinant HIV-1 Peptide HIV-2 Peptide HIV-1 Source: CDC and Prevention.
2014 CDC Recommendations Diagnostic Laboratory Testing for HIV infection in the U.S. 4 th Generation HIV-1/2 Ag/Ab Immunoassay (+) (-) Negative for HIV-1 and HIV-2 antibodies and p24 Ag HIV-1/HIV-2 Ab Differentiation Assay HIV-1 (+) HIV-2 (-) HIV-1 antibodies detected HIV-1 (-) HIV-2 (+) HIV-2 antibodies detected HIV-1 (+) HIV-2 (+) HIV antibodies detected HIV-1 (-) or Indeterminate HIV-2 (-) Source: Branson B. CDC and Prevention.
2014 CDC Recommendations Diagnostic Laboratory Testing for HIV infection in the U.S. 4 th Generation HIV-1/2 Ag/Ab Immunoassay (+) (-) Negative for HIV-1 and HIV-2 antibodies and p24 Ag HIV-1/HIV-2 Ab Differentiation Assay HIV-1 (+) HIV-2 (-) HIV-1 antibodies detected HIV-1 (-) HIV-2 (+) HIV-2 antibodies detected HIV-1 (+) HIV-2 (+) HIV antibodies detected HIV-1 (-) or Indeterminate HIV-2 (-) HIV-1 RNA Source: Branson B. CDC and Prevention.
2014 CDC Recommendations Diagnostic Laboratory Testing for HIV infection in the U.S. 4 th Generation HIV-1/2 Ag/Ab Immunoassay (+) (-) Negative for HIV-1 and HIV-2 antibodies and p24 Ag HIV-1/HIV-2 Ab Differentiation Assay HIV-1 (+) HIV-2 (-) HIV-1 antibodies detected HIV-1 (-) HIV-2 (+) HIV-2 antibodies detected HIV-1 (+) HIV-2 (+) HIV antibodies detected HIV-1 (-) or Indeterminate HIV-2 (-) HIV-1 RNA HIV-1 RNA (+) HIV-1 RNA (-) Acute HIV-1 infection Negative for HIV-1 Source: Branson B. CDC and Prevention.
HIV 2015 UPDATE New Antiretrovirals
FDA approved August 2014 Triumeq Dolutegravir + Abacavir + Lamivudine Advantages: - Another single pill regimen - Only once daily regimen without tenofovir (option if renal toxicity or osteoporosis) - Few side effects - Potency & high barrier to drug resistance Issues: - Need HLA B5701 testing prior to starting - Studies with Efavirenz or PIs questioned efficacy of Epzicom (abacavir/ lamivudine) in persons with a viral load >100,000 copies/ml - Controversial effect of abacavir on cardiac risk
Dolutegravir + ABC-3TC versus Efavirenz-TDF-FTC SINGLE Study: Result Week 48 Virologic Response Patients (%) with HIV RNA < 50 copies/ml 100 80 60 40 20 Dolutegravir + Abacavir-Lamivudine Efavirenz-Tenofovir-Emtricitabine 88 90 81 83 83 76 0 All 100,000 copies/ml > 100,000 copies/ml Baseline HIV RNA Source: Walmsley SL, et al. N Engl J Med. 2013;369;1807-18.
Cobicistat-Boosted Protease Inhibitors FDA approved January 2015 Prezcobix: Darunavir (Prezista) + Cobicistat Evotaz: Atazanavir (Reyataz) + Cobicistat Advantages: - First alternative to ritonavir for boosting (option of unable to tolerate) - Decrease pill burden if on boosted darunavir or boosted atazanavir Issues: - GI issues for many patients, similar to ritonavir - Also has similar drug-drug interactions with p450 meds - Blocks creatinine secretion, complicating estimation of renal function
Effect of Cobicistat on Creatinine Bowman s Capsule Proximal Tubule Distal Tubule Multidrug and Toxin Extrusion Efflux Proteins (MATE) Cobicistat Inhibits tubular secretion of creatinine via inhibition of MATE1 Collecting Tubule Loop of Henle Excretion Source: German P, et al. J Acquir Immune Defic Syndr. 2012:61:32-40.
Tenofovir Alafenamide Fumarate (TAF) Investigational - Elvitegravir/cobicistat/emtricitabine/TAF Pro-drug of tenofovir diphosphate (tenofovir DP) Current tenofovir product: tenofovir disoproxil fumarate (TDF) also pro-drug - Converted to tenofovir DP in the blood Advantages: - TAF converted to tenofovir DP intracellularly - Less toxicity renal and bone - Lower mg dosage facilitates co-formulation Issues: - Cost increases
HIV 2015 UPDATE 2014 HHS Antiretroviral Therapy Guidelines
US Health and Human Services (HHS) November 13, 2014 Antiretroviral Therapy Guidelines Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents Developed by the HHS Panel on Antiretroviral Guidelines for Adults and Adolescents A Working Group of the Office of AIDS Research Advisory Council (OARAC) Source: 2014 HHS Antiretroviral Therapy Guidelines. AIDS Info (www.aidsinfo.nih.gov)
Updated HIV Care Cascade in United States 100% 82% 66% 37% 33% 25% Source: Hall HI, et al XIX IAC; July 22-27, Washington DC. Abs FRLBX05
Initiating Antiretroviral Therapy
At what CD4 cell count would you consider HAART? A. < 100 cells/mm 3 B. < 200 cells/mm 3 C. < 350 cells/mm 3 D. < 500 cells/mm 3 E. Any CD4 cell count
ANTIRETROVIRAL THERAPY: DHHS GUIDELINES DHHS Antiretroviral Therapy Guidelines: Nov 2014 Factors Affecting Decision on When to Initiate Therapy More effective regimens More convenient regimens Better tolerated therapy Less long-term toxicity Better immune recovery Lower rates of resistance More treatment options Concerns for uncontrolled viremia Decrease HIV transmission Earlier Therapy Lack of RCT data supporting early Rx Potential drug toxicity Drug and monitoring cost Potential negative impact on QOL Later Therapy
HIV Prevention Trials Network (HPTN) Study 052 1,763 HIV Serodiscordant Couples (97% heterosexual) + - + - + - + - n = 872 n = 853 n = 37 n = 1 Source: Cohen M, et al. N Engl J Med. 2011;36:493-505.
ANTIRETROVIRAL THERAPY: DHHS GUIDELINES HIV Prevention Trials Network (HPTN) Study 052 1000 1,763 HIV Serodiscordant Couples (97% heterosexual) CD4 Cell Count 800 600 400 Early Therapy CD4 350-550 cells/mm 3 550 350 200! Deferred Therapy CD4 < 250 cells/mm 3 or AIDS Related Event 250 0 Source: Cohen M, et al. N Engl J Med. 2011;36:493-505.
HIV Prevention Trials Network (HPTN) Study 052 96% Reduction Early Therapy (n = 886) 1 P < 0.001 Deferred Therapy (n = 877) 27 0 5 10 15 20 25 30 Linked Transmissions Source: Cohen M, et al. N Engl J Med. 2011;36:493-505.
PARTNER Study 767 HIV Serodiscordant Couples Heterosexual MSM + - + - + - n = 445 n = 282 Source: Rodger A, et al. Abstract 153LB. 21st CROI, March 4-6, 2014.
PARTNER Study HIV+ partner on HAART and VL <200 copies/ml Only data from couples who reported sex without condoms were included in analysis Grand total of 44,439 sex acts HIV transmission did occur, but only from OUTSIDE partners None were phylogenetically linked to the original HIV+ in any couple Transmission rate = 0 However, longer-term transmission risk with suppressive ART may NOT be zero Source: Rodger A, et al. Abstract 153LB. 21st CROI, March 4-6, 2014.
HIV Prevention
Pre-Exposure Prophylaxis (PrEP) Daily antivirals to reduce risk of sexually acquired HIV infection in adults HIV negative person FDA approved tenofovir/emtricitabine for PrEP July 2012 Safe Effective: Reduces HIV acquisition by ~60-85% No evidence of risk compensation in clinical trials
HIV 2014 UPDATE Importance of Adherence
Adherence v. Non-Adherence Medication adherence = extent patient takes a medication in the way intended by health care provider Non-adherence is meant to be non-judgmental, not an expression of blame Typical adherence rates for long-term medications are 50-75% 100% adherence often the expectation in prison/jail HIV viral suppression require good adherence
How would you estimate your adherence?
How would you esdmate your adherence? A. 20% B. 50% C. 70% D. 80% E. 90% F. 95% G. 100%
Predictors of Adherence Treatment Regimen: - #pills, dosing frequency, food requirements, med side effects Disease Characteristics: - Stage & duration of HIV, opportunistic infections, HIV symptoms Patient Provider Relationship - Overall satisfaction & trust Clinical Setting - Perceived confidentiality - Prior experiences with correctional health care system Patient Variables - Sociodemographic factors - Psychosocial factors: MH, substance use, lack of knowledge
MAXIMIZING ADHERENCE DURING INCARCERATION Maximizing Adherence in Corrections Medication dispensation Medication access Dealing with custodial barriers Minimizing patient barriers
MAXIMIZING ADHERENCE DURING INCARCERATION Keep on Person (KOP) vs. Pill Line (DOT) KOP! Avoids waiting time in line Doesn t interrupt activities You aren t seen on the line and questioned by others Develops self-sufficiency which may facilitate adherence upon release Pill Line! Helps some to remember More interaction with medical staff Distrust of cellie Avoids issues with cell and strip searches Can track adherence
Which method of medicadon dispensadon leads to beoer adherence? A. Keep on Person (KOP) B. Pill Line
MAXIMIZING ADHERENCE DURING INCARCERATION Adherence and Method of Medication Dispensation % ART Adherence 100 90 80 70 60 50 40 30 20 10 0 90 92 86 89 90 82 Overall DOT SAT/KOP MEMS Pill Count Adherence overall was high compared to the community Directly observed therapy (DOT) did not improve adherence Majority (68%) reported they prefer self-administered therapy (SAT) to DOT Source: Wohl DA, et al. Clin Infect Dis. 2003;36(12):1572-76.
HIV 2014 UPDATE Patient Barriers to Adherence
Patient Barriers Distrust of the system Concern about confidentiality Frequency of dosing & pill burden Side effects Co-morbidities - Mental health issues (& stigma) - Addiction - Viral hepatitis
Distrust of the System
You suggest patient start HAART & they say, I ain t taking any of those meds in prison. I don t want to be a guinea pig for some experimental drugs. I ll never get the same stuff Magic Johnson takes anyway. You respond 1. I m not going to waste my time seeing you, if you aren t interested in following what I recommend. Don t come back until you change your attitude. 2. It s your choice, but you ll have to sign this refusal of treatment form. Kite me if you change your mind. 3. I m glad to see you care about your health. I would like to continue discussing the possible med options available & will see you back regularly to answer any questions you have.
Establish Trust Trust is earned and takes time, especially for offenders Build rapport Educate!!! - Illiteracy & low reading level common - Use diagrams & pictures - Consider peer support Collaborate allow the offender as much control of the situation as possible
Confidentiality
Maximize Confidentiality Avoid segregating HIV offenders Avoid having an HIV provider Don t group on a call out list When possible, have auditory privacy - Close doors - Have officers stand out of ear shot - Don t talk about patients in hallways or public places - Use no contact rooms Maintain privacy of records - No papers with patient info on desk - Angle computer screens - Proper email use (e.g. forwarding indentifying info) Instruct not to disclose personal info in kites Use professional translators
Recommended Antiretroviral Regimens
HHS Antiretroviral Therapy Guidelines: 2014 Recommended Regimens Regardless of Viral Load for ARV-Naïve Patients Class Therapy Pill Burden NNRTI-Based PI-Based Efavirenz-Tenofovir-Emtricitabine Atazanavir + Ritonavir + Tenofovir-Emtricitabine Darunavir + Ritonavir + Tenofovir-Emtricitabine Raltegravir + Tenofovir-Emtricitabine INSTI-Based Elvitegravir-Cobicistat-Tenofovir-Emtricitabine Dolutegravir-Abacavir-Lamivudine Dolutegravir + Tenofovir-Emtricitabine * Abacavir recommended only if HLA-B5701 negative Source: 2014 HHS Antiretroviral Therapy Guidelines. AIDS Info (www.aidsinfo.nih.gov)
HHS Antiretroviral Therapy Guidelines: 2014 Recommended Regimens Only if Viral Load <100,000 copies/ml Class Therapy Pill Burden Ŧ Rilpivirine-Tenofovir-Emtricitabine NNRTI-Based Efavirenz + *Abacavir-Lamivudine PI-Based Atazanavir + Ritonavir + *Abacavir-Lamivudine Ŧ Recommended only if CD4 count >200 cells/ml *Abacavir recommended only if HLA-B5701 negative Source: 2014 HHS Antiretroviral Therapy Guidelines. AIDS Info (www.aidsinfo.nih.gov)
Suggested Wholesale Price of Brand and Generic ARVs Monthly Cost Abacavir $670 $603 Brand Drug Didanosine $369 $478 Generic Drug Lamivudine $423 $499 Stavudine $403 $512 Zidovudine $361 $558 Zidovudine- Lamivudine $932 $1,082 Nevirapine $670 $651 0 200 400 600 800 1000 1200 Monthly Cost Source: 2013 HHS Antiretroviral Therapy Guidelines. AIDS Info (www.aidsinfo.nih.gov)
HHS Antiretroviral Therapy Guidelines: March 2012 Factors to Consider for HIV Treatment Regimen selection should be individualized & based on many factors: Comorbid conditions - (e.g., cardiovascular, liver or renal disease, drug use, mental illness, TB) Potential adverse drug effects Potential drug interactions with other medications Pregnancy or pregnancy potential Genotypic drug-resistance testing Specific drug issues Patient adherence potential Convenience (e.g., pill burden, dosing freq, & food considerations) Source: 2012 HHS Antiretroviral Therapy Guidelines. AIDS Info (www.aidsinfo.nih.gov)
Single Tablet Regimens
Single Tablet Antiretroviral Regimens AWP (Monthly) Efavirenz-Tenofovir-Emtricitabine $2402 Rilpivirine-Tenofovir-Emtricitabine Elvitegravir-Cobicistat-Tenofovir-Emtricitabine Atripla Complera Stribild $2463 $2949 Dolutegravir-Abacavir-Lamivudine Triumeq $2649 AWP = Average Wholesale Price (Monthly): 2014 HHS Antiretroviral Therapy Guidelines
HIV MEDICATION ADHERENCE Monitoring Adherence During Incarceration
You are told by pharmacy that one of your HIV patients repeatedly picks up his refills late. You are concerned about his non-adherence, so 1. You take them off HAART immediately They don t deserve it 2. You make all his HIV medications pill line until he can prove he can take them regularly 3. You make him LWOP 4. You call out patient & discuss barriers to taking the meds daily & ways to minimize them
MONITORING ADHERENCE DURING INCARCERATION Ways to Monitor Adherence Patient self-report - Accurate self-reporting requires collaborative and non-judgmental relationship - Example conversation: Taking pills every day is really hard. Most people have problems taking their pills at some point during treatment. I would like to know if you have had any problems with taking your pills, missing pills, or taking them late. I am asking because I want to help figure out ways to make it easier for you to take them. Unannounced pill count in cell - If done by custody, this may not engender trust - Extra pills in cell = lack of adherence Pill line - Monitors adherence, but does not necessarily improve adherence HIV viral load
Monitoring CD4 Cell Count Initiation of therapy Need for prophylaxis against OI Once suppressed for 2 years - CD4 300-500 cells: Every 12 months - CD4 > 500 cells: Optional Virologic rebound HIV-associated clinical symptoms Development of conditions that may reduce CD4 count Source: 2014 HHS Antiretroviral Therapy Guidelines. AIDS Info (www.aidsinfo.nih.gov)
Questions?!