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HIV? CHOLHUA, March 2015 Jean-Marc Fix, FSA, MAAA, VP, R&D.

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Presentation on theme: "HIV? CHOLHUA, March 2015 Jean-Marc Fix, FSA, MAAA, VP, R&D."— Presentation transcript:

1 HIV? CHOLHUA, March 2015 Jean-Marc Fix, FSA, MAAA, VP, R&D

2 2 Why not? The End

3 Is a segment of the HIV-infected population insurable? CHOLHUA, March 2015 Jean-Marc Fix, FSA, MAAA, VP, R&D

4 4 Agenda What is HIV infection? Evolution of HIV infection mortality Evolution of HIV infection treatment Segmentation of HIV-infected population Mortality of the better segments Underwriting skills Unknowns and risk mitigation strategies

5 5 Face of a killer

6 6

7 7

8 8

9 9

10 10 A Close-up

11 11 Video- Infection https://www.youtube.com/watch?v=RO8 MP3wMvqghttps://www.youtube.com/watch?v=RO8 MP3wMvqg 4’08”

12 12 Infectious pathway Men having sex with men Heterosexual Intravenous drug user Blood product (transfusion, hemophilia) Occupational

13 13 Infectious pathway -Men Source: HIV AIDS Surveillance vol 19 CDC

14 14 Infectious pathway - Women Source: HIV AIDS Surveillance vol 19 CDC

15 15 What kills? Depletion of CD4+ T helper cells Loss of immune protection AIDS defining diseases ~50% (1) Liver disease (hepatitis co-infection) Infection (non AIDS defining) Cancer (non AIDS defining) Cardiovascular Drug overdose, accident, suicide Source: Gill et al, Clin Infect Dis 2010

16 What we remember AIDS Is Top Cause of Death for Young Adults in U.S. Disturbing report by federal agency San Francisco Chronicle 2/1/95 Together in Life and Death San Ramon pair die of AIDS 2 days apart… Ray, 58, and Peggy, 54, of San Ramon, died earlier this month after battling the disease for five years. They were buried Monday in the same grave. SFC 2/1/95 Hunting for the Hidden Killers: AIDS Time Magazine 7/4/

17 Número estimado de adultos y niños que vivían con el VIH en 2008 Total: 33,4 millones (31,1 – 35,8 millones) Europa occidental y central [ – ] África del Norte y Oriente Medio [ – ] África subsahariana 22,4 millones [20,8 – 24,1 millones] Europa oriental y Asia central 1,5 millones [1,4 – 1,7 millones] Asia meridional y sudoriental 3,8 millones [3,4 – 4,3 millones] Oceanía [ – ] América del Norte 1,4 millones [1,2 – 1,6 millones] Caribe [ – ] América Latina 2,0 millones [1,8 – 2,2 millones] Asia oriental [ – 1,0 millones]

18 18 HIV mortality

19 19 HIV deaths

20 20 What we should be hearing Managing HIV as a Chronic Disease South Afr j of HIV Med 2004 When AIDS became a chronic disease West J Med 2000 HIV: Now a Manageable Chronic Disease Pharmacy Times 2007 Comprehensive Clinical Care: Managing HIV as a Chronic Illness AIDS Clinical Care Journalwatch retrieved July 2010

21 21 HIV mortality

22 Trends in Annual Age-Adjusted* Rate of Death Due to HIV Infection, United States, 1987−2010 Note: For comparison with data for 1999 and later years, data for 1987−1998 were modified to account for ICD-10 rules instead of ICD-9 rules. *Standard: age distribution of 2000 US population

23 23 Advances in treatment Source: Pallella et al, J Acq Immune Def Syndr 2006

24 24 HAART Highly Active Antiretroviral Treatment Latest is triple cocktail, for ART naïve patients: –NNRTI + 2 NRTI: Atripla and Complera –Ritonavir boosted PI + 2 NRTI –INSTI + 2 NRTI NRTI = nuclesos(t)ide reverse transcriptase inhibitor NNRTI = non-nucleoside reverse trans. inhib. PI = protease inhib. INSTI = integrase strand transfer inhib. Source: Guidelines for the use of antiretroviral agents in HIV-1 infected adults and adolescents DHHS as of 3/15

25 25 Video-Treatment https://www.youtube.com/watch?v=RO8 MP3wMvqg 4’09”

26 26 Advances in treatment

27 27 Action path of treatment

28 28 Action path of treatment

29 29 HIV reservoirs CD4+ memory T-cell Can stay inactive and virus dormant for many years Under current therapy: 60+ years to clear the virus (1) (1): Marsden and Zack J Antimicrob Chemo 2009

30 30 Variables for mortality Age Gender Smoking Income CD4+ cell count Viral load Time since infection Response to treatment Quality of follow-up Infection source

31 31 Mortality by therapy When: Where: 8 cities in US Who:12% IDU, 12% Females, MSM decreasing to 65% Severity: All had CD4+ cell counts below 100/mm3 Significant treatment change in 1996 Source: Pallella et al NEJM 1998

32 32 Mortality by therapy RR death or morbidity Source: Pallella et al NEJM 1998 None vs. Monotherapy1.5 None vs. combo2.9 None vs. combo with protease inhibitor 4.5

33 33 Mortality evolution When: Where: 23 cohorts in Europe, Australia, Canada Who:18% IDU, 22% Females, MSM 57% Severity: Since seroconversion Follow-up: median 6.3 (range 1 day to 23.8 years) Source: Bashkaran et al, JAMA 2008

34 34 Mortality evolution Source: Bashkaran et al, JAMA 2008 Deaths Pre Expected Observed Obs/Exp

35 35 Mortality evolution Source: Bashkaran et al, JAMA 2008

36 36 Mortality evolution Source: Bashkaran et al, JAMA 2008

37 37 Mortality by age Source: adapted from Table 4, Bashkaran et al, JAMA 2008 Age at seroconversion %736% %375% %150% 45+na192% Ratio observed to expected mortality by age, 15 year after seroconversion

38 38 Mortality by segment 7 year post cART France, first treated with PI Overall: SMR 7.0 –Men 4.8 –Women 13.0 HCV status –Positive: 13.9 –Negative: 4.4 HIV transmission –IV drugs 16.3 –Other 5.5 Source: Lewden et al, J Acq Immune Def Syndr 2007

39 39 Mortality by segment Source: Lewden et al, J Acq Immune Def Syndr 2007 CD4+ count cells/mm3 SMR <

40 40 Mortality by segment Source: Lewden et al, J Acq Immune Def Syndr 2007

41 41 Mortality by age, CD4+ count and viral load Monte Carlo simulation model Includes HIV resistance evolution with treatment Calibrated from a US cohort (CHORUS, less IDU, less non-white) Validated against VA study (more IDU, more non-white) Source: Braithwaite et al, Am J of Med 2005

42 42 Modeling flowchart Source: Braithwaite et al, Am J of Med 2005

43 43 Mortality Age 30 AgeCD4+ (cells/mm^3)Viral load /mlMedian survivalMort Mult (men) , % 100, x 1,000, x 50010, x 100, x 1,000, x 20010, x 100, x 1,000, x Source: from Braithwaite et al, Am J of Med 2005

44 44 Mortality Age 40 AgeCD4+ (cells/mm^3)Viral load /mlMedian survivalMort Mult (men) , % 100, % 1,000, x 50010, % 100, x 1,000, x 20010, x 100, x 1,000, x Source: from Braithwaite et al, Am J of Med 2005

45 45 Mortality Age 50 AgeCD4+ (cells/mm^3)Viral load /mlMedian survivalMort Mult (men) , % 100, % 1,000, x 50010, % 100, % 1,000, x 20010, % 100, % 1,000, x Source: from Braithwaite et al, Am J of Med 2005

46 46 HAART treatment consequences Dyslipidemia Insulin resistance/diabetes Endothelial dysfunction Altered fat distribution More AMI in HIV + Source: Triant et al, J Clin Endocrinol Metab 2007

47 47 HAART treatment consequences Source: Triant et al, J Clin Endocrinol Metab 2007 HIV +HIV -Ratio Heart Attack Rates per 1000 PY % % % % % %

48 48 Data limitations- the bad news Atherosclerotic cardiovascular conditions take a long time to manifest themselves

49 49 Underwriting skill-the good news Cardiovascular risk: our best skill set and treating physician are now well aware of the risk Hepatitis co-infection (Hep. B &C) IDU We CAN identify the best risks

50 50 Coronary heart disease risk in HIV % increase in riskHIV+ 1HIV+ 2HIV – (7) Age - per year 9%6%6-9% Sex – M vs F N/A110% % Diabetes – Yes vs No 260%90% % Smoking – Yes vs No 140%290%70-290% Hypertension – Yes vs No 30%80%80-90% Tot Chol - per 1mmol/L N/A26%25-33% HDL chol. - per 1mmol/L N/A-28%-52% Source: Schambelan et al, Circulation 2008

51 51 The best Age: older is better Behavior: no drugs, how HIV acquired Income: higher is better HIV characteristics: CD4+ cell count and viral load Treatment: timing, quality, response, follow-up, adherence Documentation: available and plentiful

52 52 Unknowns and risk mitigation strategies Full underwriting Shorter term or shorter term equivalent coverage? Limit the face amount Reinsure

53 53 Potential Treatment Venues Don’t get infected Kill the virus Prevent entry of the virus in the cell Prevent normal virus intracellular processes Prevent viability of cell produced virus Kill infected active cells Kill infected latent cells Prevent CD4+ cell depletion

54 54 Kill the Virus Immune response boosters: –cytokines, –interferon, –monoclonal antibodies, –vaccine, –gene therapy

55 55 Prevent Virus Entry Prevent entry of the virus –Block access on T cell CD4 CCR5 CXCR4 –Block connectors from virus –Block fusion –Cleave connectors: abzyme

56 56 Prevent Normal Virus Process Viral decay accelerator Innate antiretroviral factor

57 57 Prevent viability of cell produced virus Maturation inhibitors –Env targeted cytotoxin ( Berger 6/10 ) –Gag cleavage ( Adamson, 8/09 ) –CA-CA interaction ( ibid. ) Zinc finger inhibitors

58 58 Maybe one day Kill infected active cells Kill infected latent cells Prevent CD4+ cell depletion Gene therapy Vaccine

59 59 Updates Better understanding of CD4 cell death due to HIV infection of nearby cells and drug blocking that death and an existing drug blocking that effect ( Doitsh, Nature 2013 ) In monkeys, gene therapy ups the natural defenses against HIV ( Gardner, Nature 2015 )

60 Questions? 60


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