HIV A 2017 Update Bill Rooney MD SCOR Global Life

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1 NHOLUA November 14, 2017 HIV A 2017 Update Bill Rooney MD SCOR Global Life

Agenda 1 2 3 4 5 The Immune System HIV the illness Prevalence Diagnosis Natural Course Treatment A look at 100 HIV

2 Agenda The Immune System HIV the illness Prevalence Diagnosis Natural Course Treatment A look at 100 HIV patients Changing mortality since ART was introduced Application of what we have discussed today to life insurance 2

3 T Helper Cells Stimulation Antigen MHC receptor Antigen presenting cell (APC) T Helper Cell B Cell Antibodies Killer T cell Lymphocyte - Light Microscope Lymphocyte - Electron Microscope Macrophage 3

Cell (Bacteria) being attacked by virus https://en.wikipedia.

4 Cell (Bacteria) being attacked by virus Accessed 11/10/2017 by using Google usage Right labeled for reuse with modification 4

Viruses Type: RNA versus DNA SS versus DS Envelope versus non-enveloped Transmission: Arthropods Droplet contact Fecal-oral Sexual Vertical Blood Breast milk Location of infection: GI/Liver

5 Viruses Type: RNA versus DNA SS versus DS Envelope versus non-enveloped Transmission: Arthropods Droplet contact Fecal-oral Sexual Vertical Blood Breast milk Location of infection: GI/Liver Respiratory Brain Nerves Sexual organs Blood Consequences: Infection then resolution including immunity Chronic infection Cancer Different Viruses: 1,300 viruses have had their entire genome sequenced. (2015 data) 12,500 new viruses just recently discovered 5

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6 HIV id5eqjxwiaw&url=https%3a%2f%2fcommons.wikimedia.org%2fwiki%2ffile%3ahi-virion-en- 2.png&psig=AFQjCNFcyzRV1fDpYKqp9ITfVuOwIfoBKw&ust= retrieved 6/8/17 using Google s Labeled for reuse with modification filter retrieved 6/8/17 using Google s Labeled for reuse with modification filter 6

7 HIV HIV is a retrovirus type RNA virus. It enters a human cell along with reverse transcriptase and gets incorporated into the human DNA It then causes the cell to make additional RNA virus particles It attacks the cells of the human immune system such as helper T cells (specifically those called CD4 T cells) Lymphocyte HIV virus The infection causes a progressive deterioration of the immune system demonstrated by gradually decreasing CD4 cells Cancers and opportunistic infections occur 7

8 The History of HIV 1981 Cluster (5) of Pneumocystis carinii pneumonia and Kaposi s sarcoma cases in LA described by the CDC in June. By Dec report of over 270 similar cases reported across the US ID of the cytopathic retrovirus Serologic test for HIV available Antiretroviral drugs introduced Combination antiretroviral therapy (ART) begun 1999 Mortality, AIDS, AIDS-defining diagnosis, and hospitalizations all down 60-80% since 3 years earlier when ART use began 8

9 The History of HIV 2012 FDA Approves the use of Truvada for pre-exposure prophylaxis (PrEP) SCOR Develops an underwriting model that enables its customers to offer life insurance to HIV positive lives in Africa. First HIV positive client reinsured in CDC Announces that only 30% of Americans with HIV had the virus under control in /3 s of those out of control had been diagnosed but are no longer in care. Conference on Retroviruses and Opportunistic Infections report A man taking Truvada has contracted HIV. This is the first reported infection of someone regularly taking the drug. SCOR announces that as of 1/3/2016 The total # of lives underwritten is..3,273 Terms offered to 89% of all lives underwritten Similar acceptance rates as CAD, DM, and cancer cases The total # of claims in HIV + patients is.0 9

Stages of HIV Acute HIV infection 0-6 months typically 10-60% of people will not experience symptoms The usual time for symptoms (if developed) is 2-4 weeks after exposure Chronic HIV infection 6

10 Stages of HIV Acute HIV infection 0-6 months typically 10-60% of people will not experience symptoms The usual time for symptoms (if developed) is 2-4 weeks after exposure Chronic HIV infection 6 months to 10 years typically (without treatment) Either: Asymptomatic Early symptomatic HIV infection (formerly known as AIDS-related complex) AIDS Without treatment typically death occurs in ~3 years Either or Both: CD4 cell count <200 cells/microl AIDS-defining condition 10

11 The Symptoms of acute HIV Pulmonary symptoms not common 11

12 Acute infections associated with acute HIV infection 12

13 Acute infections associated with acute HIV infection 13

AIDS CD4 cell count <200 cells/microl OR The presence of an AIDSdefining condition Opportunistic Infection Malignancy Other conditions Includes:

disease (other than liver, spleen, or nodes) Mycobacterium avium complex (disseminated or extrapulmonary) Mycobacterium tuberculosis (any site) Others

14 AIDS CD4 cell count <200 cells/microl OR The presence of an AIDSdefining condition Opportunistic Infection Malignancy Other conditions Includes: Pneumocystic jiroveci pneumonia Esophageal Candidiasis Coccidiomycosis (disseminated or extra pulmonary) Cryptococcus (extrapulmonary) Cytomegalovirus disease (other than liver, spleen, or nodes) Mycobacterium avium complex (disseminated or extrapulmonary) Mycobacterium tuberculosis (any site) Others Includes: Kaposi sarcoma Lymphoma, Burkitt (or equivalent term) Lymphoma, primary of brain Others Includes: Wasting syndrome attributed to HIV Encephalopathy, HIV related Others 14

15 HIV Prevalence WORLDWIDE HIV DISTRIBUTION SUB SAHARAN AFRICA, EXCLUDING SOUTH AFRICA SOUTH AFRICA ASIA AND THE PACIFIC WESTERN AND CENTRAL EUROPE AND NORTH AMERICA LATIN AMERICA EASTERN EUROPE AND CENTRAL ASIA MIDDLE EAST AND NORTH AFRICA THE CARRIBEAN US DATA from the CDC 1 : In Dec, 2014 there were 955,081 people living with diagnosed HIV infection in the US Those with stage 3 (AIDS) classification: 18,303 Those ever classified with stage 3 (AIDS) classification: 521,

16 HIV Incidence United States New Cases by Subpopulation ~1 in 8 people are living with HIV and don t know it The number of new HIV diagnosed cases declined by 19% in the last decade 16

17 HIV Incidence United States HIV New Cases By Age 17

? 87% IV Drugs 13% What percentage overall is IV drug use associated with HIV acquisition?

18 HIV Incidence United States A few questions followed by answers Gay and bisexual men account for what % of HIV diagnosed males?? 83% Of women who have HIV, what % are from heterosexual contact?? 87% IV Drugs 13% What percentage overall is IV drug use associated with HIV acquisition?? 6% The rate of decline is 19% like previously stated. What % decrease in women acquiring HIV?? 40% 18

received treatment and been viral load tested.

19 100 HIV Positive Americans (2011 CDC data) 14 Unaware 46 not getting care 40 getting care 37 prescribed ART 30 compliant with sustained undetectable viral loads WHO Data Goal is In 2016 only 42% of people on ART globally were estimated to have received treatment and been viral load tested. Of those 82% had viral load suppression % varied by age range y/o 13% % % >65 37% This % is stable (26% in 2009) Retrieved 6/7/

20 Natural history prior to ART Viral Count 30,000 to 50,000 copies/ml Average life expectancy 10 years. Long-term non-progressors A minority of HIV patients (~13%) Do not develop clinical progression Have stable CD4 counts Have low levels of viremia (<10,000 copies) These individuals still are at risk for CV disease and other noninfectious complications CD 4 count drops 50/mm3 per year Opportunistic infections are common once CD4 count is <100. Pneumocystis pneumonia ~50% chance in 1 year Once the CD4 count drops to <50 Average Life Expectancy is months 20

Normal non-infected individual ~1000 cells/microl Range from 500 1,500 cells in healthy individuals HIV + individual Gradual progressive decline in count Rate of decline correlates with viral count

21 Normal non-infected individual ~1000 cells/microl Range from 500 1,500 cells in healthy individuals HIV + individual Gradual progressive decline in count Rate of decline correlates with viral count 4% per year per log copies/ml of HIV RNA HIV acquisition ~6 months ~12 months ~14.5 months CD 4 count decline After ~1 year pace of decline slows to cells (average ~50) decreased per year but dependent on viral count as above 21

22 HIV Testing Recommendations Prior to 2006 risk-based screening was recommended BUT: ~15% of people + for HIV don t know they are infected SO: In 2006 the CDC recommended routine voluntary HIV screening for all individuals aged ME TOO: Other organizations have issued similar recommendations since then (e.g. ACP, USPSTF) THE TEST: Typical testing is with a 4th generation Ag/Ab combo HIV immunoassay IF AN EARLY INFECTION IS SUSPECTED: an HIV RNA test is also performed. 22

23 HIV testing in 2017 Titer HIV RNA (plasma) Viral detection Nucleic acid test 50 copies/ml 10 days 1-5 copies/ml 5 days Includes HIV-1 Ab HIV-2 Ab HIV-1 p24 Ag HIV Antibody HIV p24 Antigen Western Blot d for indeterminate for positive Level of Detection th generation Ab/Ag 2 nd generation immunoassay 1 st generation immunoassay HIV acquisition Days after infection 23

24 Home Testing Walgreen s sells a Home HIV test blood test (~$38.00) Lancet used to obtain blood Send in the specimen to the lab 99.9% accuracy Walgreen s also sells a oral in-home test (~$44.00) Swab the cheek or gums Place the swab into the test tube Answer in 20 minutes If + needs confirmatory test One source cites a 92% sensitivity when used by a patient (99% when done by a trained professional) 24

25 Treatment of HIV -- Current DNA HIV virus RNA Receptor Human Cell Available medications for HIV 25 different antiretroviral medications 6 different major classes 25

Treatment of HIV -- Current Protease inhibitors Atazanavir Darunavir Lopinavir Nucleoside reverse transcriptase inhibitors Tenofovir Emtricitabine

26 Treatment of HIV -- Current Protease inhibitors Atazanavir Darunavir Lopinavir Nucleoside reverse transcriptase inhibitors Tenofovir Emtricitabine Abacavir Lamivudine Zidovudine Entry inhibitors Enfuvirtide Maraviroc Integrase strand transfer inhibitors Raltegravir Elvitegravir Dolutegravir 26

27 Treatment of HIV -- Current TERMS to know: (these terms are interchangeable) (ART) Anti-retroviral therapy (HAART) Highly active anti-retroviral therapy (cart) Combination anti-retroviral therapy Potent three-drug anti-retroviral therapy (ART) is recommended for those with HIV infection regardless of CD4 count. Once started it is continued indefinitely Anti-retroviral therapy (ART): Suppresses serum viral RNA levels Increases CD4 counts. Recommended as of 2012 by the US Dpt of Health and Human Services It also dramatically decreases the risk of viral transmission In one study 1 ART resulted in: 97% of those who had recently become infected to have undetectable viral levels at 11 weeks. 92% maintained virological suppression at 18 months. CD4 counts went from mean of 422 cells/mm 3 to 702 cells/mm 3 ART decreases Mortality Progression to AIDS Opportunistic infections Hospitalizations Mortality related to comorbid conditions (CAD, liver disease, nephropathy) 27

28 Treatment of HIV -- Current Common regimens include: Efavirenz-emtricitabine-tenofovir Rilpivirine-emtricitabine-tenofovir Elvitegravir-cobicistat-tenofovir-emtricitabine Truvada is tenofovir-emtricitabine and requires a third agent to be considered ART for treatment. Challenges with ART treatment: Drug toxicity Emergence of viral drug resistance Adverse drug to drug interactions High cost Inconvenience of taking medications daily Nonadherence GI CNS Hepatic Lipid abnormalities Increased transaminases Decreased renal function Especially prevalent with low adherence rates 28

29 Treatment of HIV--Current BREAKING NEWS NEWS RELEASE July WHO urges action against HIV drug resistance threat 6 of the 11 countries surveyed in Africa, Asia, and Latin America have recently reached the 10% threshold for resistance to some of the most widely used HIV medicines Once the 10% threshold is met WHO recommends urgently reviewing their HIV treatment programs 29

30 Mortality In 2013, HIV was the 8 th leading cause of death in those aged th for those aged th for those aged

31 Mortality 31

32 Mortality 32

33 Mortality Incidence of the diseases in the US: DM: 29.1 million people HIV: 1 million PDD*: 3.3 million *Persistent Depressive Disorder 33

34 Mortality 34

35 Increased mortality in HIV positive people Despite successful ART treatment Despite ART treatment HIV-positive patients have increased mortality when compared to HIV-negative patients CV Risk: Malignancy Risk: Other Risk: Liver disease Kidney disease Neurologic disease 35

36 Mortality Gap HIV-infected vs HIV-Uninfected Kaiser Study 24,768 HIV-infected Deaths/100,00 0 person years Life Expectancies at age 20 HIV - Uninfected HIV - infected HIV - Uninfected HIV - infected NOTE: Worse outcome observed for those with any of the following: Smoking Drug/alcohol abuse history Marcus et al. Narrowing the Gap in Life Expectancy Between HIV-Infected and HIV-Uninfected Individuals With Access to Care. J Acquir Hx. Immune of Hepatitis Defic Syndrome; B 2016 or CSep Accessed 6/21/

37 Mortality data in HIV positive people (Undergoing ART treatment) Collaborative analysis of 13 HIV cohort studies 85% of deaths had a definitive cause 39,272 patients 154,667 person years of f/u 1876 deaths 1.5 fold increase in CV risk compared to those without HIV 49.5% AIDS related 11.8% non-aids malignancies 8.2% non-aids infections 7.9% CV related 7.7% violence and/or drug 7% related liver disease Increased Atherogenesis Endothelial dysfunction Coagulation abnormalities Rates of each cause of death higher with IV drug use as the presumed transmission mode Causes of Death in HIV=1-Infected Patients Treated with Antiretroviral Therapy, Collaborative Analysis of 13 HIV Cohort Studies. Clin Infect Dis 2010 May 15; 50(10):

38 Accelerated Aging in HIV patients? 38

Epigenetics: Methylation example A G C Epigenetics: The study of how

Instead of gene sequence disturbances the impact of epigenetics is with

base cytosine at CpG sites Image from: https://en.wikipedia.

39 Epigenetics: Methylation example A G C Epigenetics: The study of how environmental factors impact gene expression. Instead of gene sequence disturbances the impact of epigenetics is with turning off or on how cells read the genes Methyl group added to the DNA base cytosine at CpG sites Image from: Accessed 9/29/15 (Bing listed as Free to modify, share, and use commercially 39

40 Increased CV Mortality Risk There is an increased risk of CV disease in HIV positive individuals when taking into consideration other known risk factors (Framingham risk factors, comorbidities, and substance abuse) Multiple studies show this however for illustration today let s look at the Veterans Aging Cohort Study published in Study from , 459 participants 27,350 HIV infected 55, 209 Uninfected AMI rates/1000 person-years Age Uninfected HIV Infected Possible mechanisms Inflammation ART medications CD4 cell count depletion Endothelial dysfunction Impaired arterial elasticity Overall, an increased hazard ratio of 1.48 Freiberg, Matthew, et al. HIV Infection and the Risk of Acute Myocardial Infarction. JAMA Intern Med 2013 April 22; 173(8):

41 Increased Malignancy Mortality Risk Malignancy Risk 88% of all cancers Incidence Cancer AIDS defining cancers Non AIDS-defining cancers Pre-ART Early ART Late ART 1985 to to to current 33% of all cancers 41

42 Malignancy Risk AIDS-defining cancers: Such as: Kaposi sarcoma Non-Hodgkin Lymphoma Invasive cervical carcinoma Cancers in those with HIV tend to: Occur at a younger age Demonstrate increased aggressiveness Present at an advanced stage Incidence has not dropped with ART Non-AIDS-defining cancers: Such as: Anal Stomach Liver Esophageal Lung Head and Neck Factors negatively impacting HIV patients: -Coinfection with other oncogenic viruses (e.g. HPV, EBV, HBV, HCV) -Immunosuppression -? Role of the antiretroviral drugs -Co-morbid conditions impact compliance/monitoring 42

43 Malignancy Risk Pre-ART Era Malignancy accounted for 10% of deaths in HIV positive Post-ART Era Malignancy accounted for 28% of deaths in HIV positive Factors involved in the increased risk of malignancy Immunosuppression HIV virus direct effect Coinfection with other oncogenic viruses? Role of the antiretroviral drugs Similar to increased malignancy risk in transplant patients chronically immunosuppressed HPV EBV HBV HHV-8 HCV Co-morbid conditions can impact compliance/monitoring 43

44 The HIV Continuum High Risk of HIV acquisition activity begins HIV Dx Made ART treatment begun CD-4 count <200 OR AIDS-defining illness ART prophylaxis begun 1 year of ART treatment completed Death Compliant with med Non-ratable CAD, mental illness, or drug/etoh abuse No IV drug use Compliant with ongoing care and ART treatment CD-4 count currently >500 Viral load undetectable No factors on a decline list which might include hx of IV drug use, concomitant Hepatitis B or C, no hx of dx of AIDS etc. 44

45 In Summary HIV impacts about 1 million American lives About 30% of HIV patients have success with sustained viral response The mortality rate has dropped significantly since ART become commonplace The CD4 count is a very useful marker Home testing is available along with traditional lab testing HIV mortality is still a concern The life insurance industry has begun insuring HIV positive lives. This will need to be monitored and adjusted as needed 45

46 HIV Questions? 46

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