Optimizing Treatment and Management of HIV/AIDS in Persons of Advanced Age

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1 Optimizing Treatment and Management of HIV/AIDS in Persons of Advanced Age This activity is jointly provided by the University of Nebraska Medical Center and Practice Point Communications Supported by an independent educational grant from Gilead Sciences Medical Affairs Simply Speaking HIV Optimizing Treatment and Management of HIV/AIDS in Persons of Advanced Age is Copyrighted 2015 by Practice Point Communications, unless otherwise noted. All rights reserved.

2 Educator John W. Hogan M.D. Washington, D.C. Disclosures - Salary: None - Royalty: None - Stock: None - Speakers Bureau: Gilead, BMS, VIIV, Janssen, Abbott - Consultant: Gilead, BMS, VIIV, Janssen, Abbott - Other: None 2

3 Program Overview Epidemiologic trends HIV screening/testing When to start therapy: mortality and prognosis Treatment options and response Management considerations 3

4 HIV/AIDS and Aging (1 of 2): NIH Statement (9/09/10) HIV clearly poses a risk to individuals 50 years and older and presents complex treatment challenges In those with long-term HIV infection, the persistent activation of immune cells by the virus likely increases the susceptibility of these individuals to inflammation-induced diseases and diminishes their capacity to fight certain diseases. Coupled with the aging process, the extended exposure of these adults to both HIV and antiretroviral drugs appears to increase their risk of illness and death from cardiovascular, bone, kidney, liver and lung disease, as well as many cancers not associated directly with HIV infection NIH statement on National HIV/AIDS and Aging Awareness Day Sept. 18,

5 HIV/AIDS and Aging (2 of 2): NIH Statement (9/09/10) HIV clearly poses a risk to individuals 50 years and older and presents complex treatment challenges HIV disease progresses more quickly in older compared with younger adults, and antiretroviral therapy restores immune system cells less effectively, placing this older group at greater risk for illness and death from HIV infection than younger people who are infected for comparable periods of time. Moreover, the higher rate of pre-existing conditions in people of advanced age often complicates their treatment for HIV infection. NIH statement on National HIV/AIDS and Aging Awareness Day Sept. 18,

6 By 2015, Approximately 50% of People Living With HIV Will Be >50 Years of Age Smith G. Senate Committee on Aging

7 NATIONAL HIV/AIDS STRATEGY UPDATED TO 2020 One of the President s top HIV/AIDS policy priorities was the development and implementation of a National HIV/AIDS Strategy (NHAS). There are four primary goals for the NHAS updated in 2015: Reducing HIV incidence Increasing access to care and optimizing health outcomes Reducing HIV-related health disparities Achieving a more coordinated national response to the HIV/AIDS epidemic 7

8 Number of New HIV Cases New HIV Cases in the US (2013): Age and Race/Ethnicity (50 States) Years of Age <20 35 to to 34 > White (n=13,101) Hispanic/Latino (n=10,117) Black (n=21,836) CDC. HIV Surveillance Report, Published February

9 Persons Living With HIV (%) Persons Living With HIV (50 States) Years of Age <20 35 to to 34 > % 35.4% 43.7% 37.7% 41.3% 40.0% % 17.4% 17.6% % 2010 (n=860,167) 1.2% 2011 (n=886,712) 1.1% 2012 (n=914,826) CDC. HIV Surveillance Report, Published February

10 Persons Living With AIDS (%) Persons Living With AIDS (50 States) Years of Age <20 35 to to 34 > % 41.4% 44.5%44.5% 41.7% 47.2% % 10.7% 10.6% 0 0.7% 2010 (n=483,972) 0.6% 2011 (n=496,584) 0.5% 2012 (n=508,845) CDC. HIV Surveillance Report, Published February

11 Years Life Expectancy Among Treated HIV Patients in the US and Canada ( ) NA-ACCORD participants >20 years of age (n=22,937) Treatment-naïve before initiating ART Crude mortality rate ( ) 19.8 per 1000 person-years (n=1622 deaths) Life expectancy at 20 years of age Increased from 36.1 to 51.4 years from to A 20-year-old HIV-positive person is expected to live into their early 70s to 2002 Life Expectancy Estimates Overall CD4 at ART initiation >350 cells/mm 3 <350 cells/mm to to 2007 NA-ACCORD: North American AIDS Cohort Collaboration on Research and Design. Samji H, et al. PLoS One. 2013;8:e

12 Issues Specific to Older Persons With HIV Disease Unprotected sex No concern about pregnancy I m too old to catch HIV Delay in testing Limited incomes Immune restoration Comorbid illnesses Polypharmacy Insufficient data on drug interactions in older population Luther VP, et al. Clin Geriatr Med. 2007;23: Illa L, et al. AIDS Behav. 2008;12:

13 Program Overview Epidemiologic trends HIV screening/testing When to start therapy: mortality and prognosis Treatment options and response Management considerations 13

14 Participants (%) National HIV Behavioral Surveillance: HIV Prevalence and Awareness of Infection Venue-based, time-space sampling of MSMs (2008, 2011) 20-city data collection system HIV prevalence 2008 (n=7847): 19% 2011 (n=8423): 18% Awareness of infection 2008 (n=1520): 56% 2011 (n=1032): 66% HIV prevalence and awareness of infection increased with age 31% increase in MSM <25 years of age Blacks Highest HIV prevalence: 30% Lowest awareness: 54% HIV Prevalence and Awareness 12% HIV prevalence Aware of being infected 49% 15% 57% 19% 67% >40 Age Group (years) 26% 76% Wejnert C, et al. PLoS One. 2013;8(10):e

15 Undiagnosed HIV (%) CDC: Estimated Prevalence of Undiagnosed HIV Infection in the United States (2006) Estimated persons living with undiagnosed HIV infection in the United States at the end of 2006 (n=232,700) 50 Undiagnosed HIV Infection 47.8% Overall incidence: 21% 40 Undiagnosed prevalence rates (per 100,000 population) % Overall: 94.2 Age (years) % 16.1% 19.1% 13-24: : : : >55: >55 Age Group (y) Campsmith ML, et al. JAIDS. 2010;53:

16 Factors Associated With Late or Missed Diagnosis of HIV Infection in Older Adults Routine screening uncommon in this age group Poor awareness of HIV risk factors (including safe sex practices) Lack of HIV prevention education targeting older adults Health care provider belief that older adults are not sexually active Failure of some health care providers to consider HIV infection in this patient population Confusion about HIV-specific or opportunistic infection symptoms with symptoms of other diseases Luther VP, et al. Clin Geriatr Med. 2007;23: Illa L, et al. AIDS Behav. 2008;12:

17 HIV Risk in Older Adults: Unprotected Sexual Activity Use of erectile dysfunction drugs contributes to increased rates of sexual activity Menopause No risk for pregnancy=no need for condom Vaginal dryness due to estrogen depletion leads to greater likelihood of trauma and increased risk of HIV acquisition Luther VP, et al. Clin Geriatr Med. 2007;23: Illa L, et al. AIDS Behav. 2008;12:

18 Project ROADMAP: Sexual Risk Behaviors of Older HIV-Positive Patients Sexually active, HIV-positive men and women Baseline demographics Age (years): 51 (45-71) Race Black (82%), Hispanic (12%), white (5%) On ART: 92% Transmission through heterosexual contact: 94% Age at HIV diagnosis Mean: 39.7 years >45 years of age: 25% Exploratory Findings Sexual preference (%) Heterosexual Homosexual Bisexual Men (n=125) Women (n=85) >1 sexual partner (%) Vaginal sex Anal sex 20 5 Number of sexual acts in past 6 months With only women (%) With only men (%) Both (%) ROADMAP: Re-educating Older Adults in Maintaining AIDS Prevention (UM/JMH). Illa L, et al. AIDS Behav. 2008;12:

19 Project ROADMAP: Sexual Risk Behaviors of Older HIV-Positive Patients Approximately 20% of sexually active participants reported not using condoms consistently 60% reported having anal or vaginal sex at least once with HIV negative/unknown serostatus partners Of these, 17.3% reported not using condoms Interventions are needed to help older patients engage in safer sexual practices ROADMAP: Re-educating Older Adults in Maintaining AIDS Prevention (UM/JMH). Illa L, et al. AIDS Behav. 2008;12:

20 Sexual Behaviors in 3 Subgroups of HIV-Positive Patients >50 Years of Age Gay/bisexual men (n=136) Heterosexual men (n=57) Number Who Were Sexually Active in Past 3 Months (%) Irregular Condom Use in Sexually Active Persons (%) Overall With Serodiscordant Partner Factors Associated With Irregular Condom Use 49 (36) Lower HIV knowledge Better cognitive functioning Lower annual income 41 (72) Increased loneliness Heterosexual women (n=97) 20 (21) Lower HIV knowledge Lovejoy TI, et al. AIDS Behav. 2008;12:

21 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 Pretest counseling not required Repeat HIV testing left to discretion of provider Based on patient risk Branson BM, et al. MMWR Recomm Rep. 2006;55(RR-14):

22 HIV Screening: Guidelines From Other Organizations US Preventive Services Task Force (2013) Strongly recommends clinicians screen for HIV in all adolescents and adults 15 to 65 years of age (endorsed by AAFP, but beginning at 18 years of age) Younger adolescents and older adults at increased risk should also be screened Recommends clinicians screen all pregnant women for HIV American College of Physicians (2008) (endorsed by the HIV Medicine Association) Recommends clinicians adopt routine screening for HIV and encourage patients to be tested Regardless of whether HIV risk factors are present Recommends clinicians determine the need for repeated screening on an individual basis US Preventive Services Task Force. AHRQ publication number EF-3. April AAFP. Qaseem A, et al. Ann Intern Med. 2009;150:

23 Additional Considerations for HIV Testing in Persons of Advanced Age Consider periodic testing in persons with continued risk If identified as being HIV positive Counsel to notify their partner(s) (sexual or injecting) Partner notification requirements vary by state law Encourage the partner to be tested for HIV Once HIV infection is established, providers should continually encourage and discuss Risk and harm reduction Safe sex practices Nguyen N, et al. Clin Interv Aging. 2008;3:

24 Program Overview Epidemiologic trends HIV screening/testing When to start therapy: mortality and prognosis Treatment options and response Management considerations 24

25 When to Start ART: Global Consensus and Diversity AIDS or CD4 Count (cells/mm 3 ) HIV-Related Symptoms < >500 United States DHHS (2015) Yes Yes Yes Yes Yes IAS-USA (2014) Yes Yes Yes Yes Yes British HIV Association (2013) Yes Yes Yes Consider Defer European AIDS Clinical Society (2014) Yes Yes Yes Consider Consider WHO (2013) Yes Yes Yes Yes Defer DHHS. Revision April 8, Günthard HF, et al. JAMA. 2014;312: EACS. Revision November BHIVA. Revision November WHO. Revision June

26 START Study: Initiation of ART in Early Asymptomatic HIV Infection Multicontinental Study (n=4685) HIV-positive adults Treatment-naive CD4 >500 cells/mm 3 Randomization 1:1 Immediate ART (n=2326) Deferred ART (n=2359) (CD4 Declined to <350 cells/mm 3 or AIDS-related event) 5//2015: DSMB recommends stopping trial: Deferred arm offered ART Primary outcome a composite outcome of 2 major components: Any serious AIDS-related event - Death from AIDS or any AIDS-defining event, Hodgkin s lymphoma Any serious non AIDS-related event - CVD (myocardial infarction, stroke, or coronary revascularization) or death from CVD, end-stage renal disease (initiation of dialysis or renal transplantation) or death from renal disease, liver disease (decompensated liver disease) or death from liver disease, non AIDS-defining cancer (except for basal-cell or squamous cell skin cancer) or death from cancer, and any death not attributable to AIDS Lundgren J, et al. 8 th IAS Conference. Vancouver, Abstract MOSY0301. The INSIGHT START Study Group. N Engl J Med. 2015;July 20. [Epub ahead of print]. 26

27 START Study: Baseline Characteristics and ART Use Both study arms were well balanced Median time since HIV diagnosis 1 year Geographical region Africa (21.3%) Asia (7.6%) Australia (2.3%) Europe and Israel (32.8%) North America (10.8%) South America and Mexico (25.1%) On ART at time of study cessation Immediate ART: 98% Deferred ART: 48% Immediate ART (n=2326) Defer ART (n=2359) Male (%) Median age (years) Median HIV RNA (copies/ml) 13,000 12,550 Median CD4 (cells/mm 3 ) Mode of HIV infection (%) MSM Person of opposite sex IDU Blood products, other Baseline Characteristics Current smoker (%) Median CHD risk at 10 years (%) Lundgren J, et al. 8 th IAS Conference. Vancouver, Abstract MOSY0301. The INSIGHT START Study Group. N Engl J Med. 2015;July 20. [Epub ahead of print]. 27

28 Number of Events START Study Outcomes: Composite Primary Endpoint and its Components Immediate ART was superior to deferral of ART Both for serious and non-serious AIDS events Majority (68%) of the primary endpoints occurred in patients with a CD4 >500 cells/mm 3 Similar significant reductions were noted across all patient subgroups No increase in adverse events associated with immediate versus deferred ART Composite Endpoint Number of Serious Events 57% Reduction (P<0.001) AIDS- Related 72% Reduction (P<0.001) 14 Deferred ART (n=2359) Immediate ART (n=2326) 47 Components (Serious Events) 29 Non-AIDS Related 39% Reduction (P=0.04) Lundgren J, et al. 8 th IAS Conference. Vancouver, Abstract MOSY0301. The INSIGHT START Study Group. N Engl J Med. 2015;July 20. [Epub ahead of print]. 28

29 Relative Risk of Death (95% CI) Relative Risk of Death (95% CI) NA-ACCORD: Risk of Death Associated With Deferred ART Baseline CD4 351 to 500 Cells/mm 3 Baseline CD4 >500 Cells/mm * ( ) 1.68* ( ) * ( ) 1.85* ( ) 1.83* ( ) ( ) 1.13 ( ) ( ) Deferral of ART Female Sex Older Age (per 10-year Increments) Baseline CD4 Count (per 100 cells/mm 3 ) 0 Deferral of ART Female Sex Older Age (per 10-year Increments) Baseline CD4 Count (per 100 cells/mm 3 ) *P<0.001 and P=0.03. Kitahata MM, et al. N Engl J Med. 2009;360:

30 Median CD4 Cell Count (cells/mm 3 ) ATHENA Cohort Study: Restoring CD4 Count to >800 cells/mm 3 National observational study 554 of 5299 previously treatment-naïve patients were on uninterrupted ART for 7 years Baseline CD4: 221 cells/mm 3 HIV RNA: 5.0 log 10 copies/ml Restoring CD4 >800 cells/mm 3 Less time to achieve and a greater proportion achieving with a higher pre- ART CD4 cell count >500 cells/mm 3 : 87% cells/mm 3 :73% cells/mm 3 : 46% 50 to 200 cells/mm 3 : 26% Achieving CD4 >800 Cells/mm 3 > <50 Baseline CD4 Strata (cells/mm 3 ) Weeks on ART Gras L, et al. JAIDS. 2007;45:

31 Program Overview Epidemiologic trends HIV screening/testing When to start therapy: mortality and prognosis Treatment options and response Management considerations 31

32 DHHS Guidelines: Regimen Classification for Treatment-Naïve Patients Recommended regimens Regardless of baseline HIV RNA or CD4 Alternative regimens Other regimen ART no longer recommended for initial therapy NRTI: zidovudine NNRTI: nevirapine PI: unboosted atazanavir, fosamprenavir or saquinavir + ritonavir Entry inhibitor: maraviroc DHHS. Revision April 8,

33 DHHS Guidelines: Recommended Regimens Regardless of Baseline HIV RNA Level or CD4 Count PI Darunavir + ritonavir (qd) + emtricitabine/tenofovir DF INSTI Raltegravir + emtricitabine/tenofovir DF Elvitegravir/cobicistat/emtricitabine/tenofovir DF* Dolutegravir /abacavir/lamivudine* Dolutegravir + emtricitabine/tenofovir DF *Available as a once-daily, single-tablet regimen. Notes: Lamivudine may substitute for emtricitabine or visa versa. Tenofovir DF: use with caution in patients with renal insufficiency. Elvitegravir/cobicistat/emtricitabine/tenofovir DF: only for patients with pre-art creatinine clearance >70 ml/min. Dolutegravir/abacavir/lamivudine: only for patients who are HLA-B*5701 negative. DHHS. Revision April 8,

34 DHHS Guidelines: Alternative Regimens May Be the Preferred Regimen for Some Patients NNRTI PI Efavirenz/emtricitabine/tenofovir DF* Rilpivirine/emtricitabine/tenofovir DF* Atazanavir/cobicistat + emtricitabine/tenofovir DF Atazanavir + ritonavir + emtricitabine/tenofovir DF Darunavir/cobicistat + emtricitabine/tenofovir DF Darunavir/cobicistat + abacavir/lamivudine Darunavir + ritonavir + abacavir/lamivudine *Available as a once-daily, single-tablet regimen. Notes: Efavirenz: avoid use in women trying to conceive or are sexually active and not using contraception. Lamivudine may substitute for emtricitabine or visa versa. Tenofovir DF: use with caution in patients with renal insufficiency. Rilpivirine/emtricitabine/tenofovir DF: only for patients with pre-art HIV RNA <100K copies/ml and CD4 >200 cells/mm 3. Atazanavir/cobicistat or darunavir/cobicistat + emtricitabine/tenofovir DF: only for patients with pre-art creatinine clearance >70 ml/min. Atazanavir + RTV: absorption depends on food and low gastric ph. Dolutegravir/cobicistat or darunavir/ritonavir + abacavir/lamivudine: only for patients who are HLA-B*5701 negative. DHHS. Revision April 8,

35 COHERE Study Collaboration of Observational HIV Epidemiological Research Europe Multi-cohort collaboration of 33 European cohorts Patients starting ART (n=67,659) Stratified by 10 age groups (<2 to >60 years of age) Pre-HAART baseline in older patients Distribution of HIV transmission categories similar with exception of IDU (lower in older versus younger patients) Higher HIV RNA levels Lower CD4 cell counts Higher percentage of AIDS diagnoses 13 to 49 years of age: 18% to 29% >50 years of age: 32% to 33% COHERE Study Group. AIDS. 2008;22:

36 HIV RNA (log 10 copies/ml) CD4 (cells/mm 3 ) COHERE Study: Baseline Virologic and Immunologic Profile by Age Baseline HIV RNA Baseline CD4 Count > >60 Age at Baseline (years) Age at Baseline (years) COHERE Study Group. AIDS. 2008;22:

37 Patients (%) Patients (%) COHERE Study: ART Response by Age HIV RNA <50 Copies/mL CD4 Gain >100 Cells/mm Years of Age 18 to 29 (n=9134) 30 to 39 (n=22,410) 40 to 49 (n=11,580) 50 to 54 (n=2693) 55 to 59 (n=1656) >60 (n=1613) Time Since ART (years) Years of Age 18 to 29 (n=9134) 30 to 39 (n=22,410) 40 to 49 (n=11,580) 50 to 54 (n=2693) 55 to 59 (n=1656) >60 (n=1613) Time Since ART (years) COHERE Study Group. AIDS. 2008;22:

38 Patients (%) Patients (%) COHERE Study: Response by Baseline Age Achieving CD4 Count >200 Cells/mm 3 at 12 Months New AIDS Event At 12 Months 100 P< for trend 12 P< for trend % 86.7% 80.5% % 8.5% 9.6% 9.3% 9.7% % 75.2% 73.9% 74.7% % 5.2% > >60 Age at Baseline (years) Age at Baseline (years) COHERE Study Group. AIDS. 2008;22:

39 Patients (%) COHERE Study: Continuation of ART by Baseline Age Similar rates of discontinuing or switching >1 antiretroviral agent during the first 12 months of ART Complete treatment discontinuation was rare Lower rates were observed among those >40 years of age Discontinuation of All ARTs at 12 Months 15.3% 14.8% 11.4% 9.2% P< for trend 6.9% 7.9% >60 Age at Baseline (years) 7.3% COHERE Study Group. AIDS. 2008;22:

40 ART and HIV in Older Persons Better adherence Similar virologic response Slower CD4 recovery in some cohorts Higher risk of progressing to AIDS Increased mortality Ledergerber B. 15 th CROI. Boston, Abstract 108. Grabar S, et al. J Antimicrob Chemother. 2006;57:4-7. Gebo KA. Drugs Aging. 2006;23: COHERE Study Group. AIDS. 2008;22:

41 Study 102: Safety Considerations by Age Groups <50 Years of Age >50 Years of Age EVG/COBI/ FTC/TDF (n=299) EFV/ FTC/TDF (n=296) EVG/COBI/ FTC/TDF (n=49) EFV/ FTC/TDF (n=56) Treatment-emergent adverse events (%) Diarrhea Nausea Abnormal dreams Dizziness Rash 28 23* 15* 8* 8* * 6* Median change in egfr (ml/min) (C-G) -13.9* * -8.2 Mean change in lipids (mg/dl) Total cholesterol LDL-C HDL-C Triglycerides +9* +10* +7* *P<0.05 versus EFV/FTC/TDF. Gallant J, et al. 53 rd ICAAC. Denver, Abstract H

42 Study 103: Safety Considerations by Age Groups <50 Years of Age >50 Years of Age EVG/COBI/ FTC/TDF (n=305) ATV/r + FTC/TDF (n=307) EVG/COBI/ FTC/TDF (n=48) ATV/r + FTC/TDF (n=48) Treatment-emergent adverse events (%) Diarrhea Nausea Depression Ocular icterus Back pain 26* * 12* Median change in egfr (ml/min) (C-G) -12.5* Mean change in lipids (mg/dl) Total cholesterol LDL-C HDL-C Triglycerides * *P<0.05 versus ATV + FTC/TDF. Gallant J, et al. 53 rd ICAAC. Denver, Abstract H

43 Program Overview Epidemiologic trends HIV screening/testing When to start therapy: mortality and prognosis Treatment options and response Management considerations 43

44 Incidence (%) CDC: HIV-Infected Persons Engaged in Selected Stages of the Continuum of Care (2009) CDC and Prevention National HIV Surveillance System 100 Age Group (years) 80 72% 85% 89% 75% 74%73% 70% 25 to to to to % > % 46% 35% 35% 28% 22% 31% 39% 42% 33% 36% 31% 27% 22% 15% 0 Diagnosed Linked to Care Retained In Care Prescribed ART Viral Suppression n=1,148,200 HIV-infected persons, 18% of whom are unaware of their infection. Hall HI, et al. JAMA Intern Med. 2013;173:

45 Patients (%) VACS Virtual Cohort: Comorbidities Among Older HIV-Infected Patients % 66% 45% Years of Age <40 (n=8522) 40 to 49 (n=14,561) (n=7225) >60 (n=3122) 40 39% 30 30% % Any Comorbidity 7% 17% 6% 2% 12% 21% 4% 1% 11% Hypertension Diabetes Vascular Disease 23% 11% 5% 7% 16% Pulmonary Disease 5% 16% 17% Liver Disease 7% 6% 1% 2%4% Renal Disease Cross-sectional analyses of patient data from the VACS virtual cohort ( ). Age was associated with all comorbidities except liver disease (P<0.001). Goulet JL, et al. Clin Infect Dis. 2007;45:

46 Patients (%) VACS Virtual Cohort: Comorbidities Among Older HIV-Infected Patients % Years of Age <40 (n=8522) 40 to 49 (n=14,561) (n=7225) >60 (n=3122) 30 28% % 24% 11% 24% 18% 16% 9% 18% 17% 5% 15% 20% 19% 9% 3% 7% 4% 2% 13% 12% 11% 6% 0 Any Substance Abuse/Dependence Disorder Alcohol Drug Any Psychiatric Disorder Schizophrenia Major Depression/ Bipolar Cross-sectional analyses of patient data from the VACS virtual cohort ( ). Goulet JL, et al. Clin Infect Dis. 2007;45:

47 CHD Incidence per 100 Patient Years CHD Incidence per 100 Patient Years Incidence of CHD: Medi-Cal Claims Data of Patients With and Without HIV Disease Men Women HIV-infected (n=20,742) Non HIV-infected (n=970,259) * * HIV-infected (n=7771) Non HIV-infected (n=2,084,437) * * * >75 Age Category (years) >75 Age Category (years) *P<0.01; P<0.05. Currier JS, et al. JAIDS. 2003;33:

48 Risk of Coronary Heart Disease in HIV-Infected Persons: Medi-Cal Database Age-specific, covariate-adjusted, relative risk of coronary heart disease by antiretroviral drug exposure Compared with treatment-naïve HIV-infected patients Adjusted for Diabetes mellitus Hyperlipidemia Kidney disease Hypertension The absolute risk of an MI is low in young patients, despite the high relative risk Relative Risk of CHD Among Treated HIV-Infected Patients Age category (y) Relative Risk (95% CI) * ( ) ( ) ( ) > ( ) *P<0.001 vs treatment-naïve HIV-infected patients. Currier JS, et al. JAIDS. 2003;33:

49 Incidence per 1000 Person-Years D:A:D Study: Incidence of Myocardial Infarction and Duration of ART Relative rate per additional year of exposure 1.16 (95% CI ) 0 Exposure (y): None < >7 No. of events No. of person-y 11, ,098 14,892 14,394 11, DAD Study Group, et al. N Engl J Med. 2007;356:

50 Abacavir and Cardiovascular Disease Risk D:A:D study SMART STEAL Quebec s Public Health Insurance database US Healthcare System cohort NA-ACCORD Association Found No Association GSK analysis FDA meta-analysis ACTG A5001 HOPS VA Clinical Case Registry NA-ACCORD No consensus on the association of abacavir and MI risk or possible mechanism for the association - Mechanistic pathways under study: endothelial dysfunction, leukocyte adhesion, inflammation, hypercoagulability Behrens GM, et al. Curr Opin Infect Dis. 2010;23:9-14. Ding X, et al. JAIDS. 2012;61: Triant VA, et al. JAIDS. 2010;15: Lichtenstein KA, et al. Clin Infect Dis. 2010;51: Cruciani M, et al. AIDS. 2011;25: Palella FJ, et al. 22 nd CROI. Seattle, Abstract 749LB. 50

51 Cardiovascular Disease and ART Accumulating data indicate that HIV-infected patients on ART may have an increased relative risk of CHD with longer exposure to therapy The excess risk may depend in part on the presence of other risk factors The role of HIV infection remains unclear 51

52 Cardiovascular Considerations in ART Modification of coronary heart disease risk and use of antiretroviral agents that are less likely to cause metabolic disturbances may be warranted when patients have many options Fear of coronary heart disease should not preclude the use of effective ART 52

53 Prevalence (%) Prevalence of Chronic Kidney Disease Among HIV Patients in Care in the US Medical Monitoring Project (2009) 2009 cross-sectional data >1 creatinine value (n=3814) CKD: egfr <60 ml/min/1.73 m 2 (MDRD) Prevalence of CKD HIV-infected adults (2009) General US population (NHANES ) Stage 3* or greater CKD: 7.6% Factors associated with CKD in HIV 25 PR: 0.8 Older age years (HR: 2.8) >60 years (HR: 7.8) 15 Female gender (HR: 1.4) 10 PR: 1.8 Longer duration of HIV infection (HR: 1.4) 5 PR: 4.6 AIDS diagnosis (HR: 2.1) CD4 <350 cells/mm 3 (HR: 1.6) PR: prevalence ratio. *Creatinine clearance (ml/min): Stage 1: >90; Stage 2: 60-90; and Stage 3,4,5: < to to 59 >60 Age Group (years) Garg S, et al. 20 th CROI. Atlanta, Abstract

54 Malignancies in HIV: Changes in Incidence Over the Past 10 Years AIDS-related malignancies Decreased Kaposi sarcoma and CNS lymphoma Increased Non-Hodgkin s lymphoma Non-AIDS-defining malignancies Overall incidence increased by >3-fold Greatest increases seen in liver, larynx, anal, and lung cancers No increase in prostate and breast cancers Mitsuyasu RT. Top HIV Med. 2008;16: Engels EA, et al. Int J Cancer. 2008;123: Patel P, et al. Ann Intern Med. 2008;148:

55 NCI: HIV Cancer Risk Among the HIV-Infected Elderly in the US ( ) Retrospective analysis of data from SEER cancer registries and Medicare claims (n=469,954) Cancer diagnoses identified through SEER (n=42,485) Cancers excluded: basal and squamous cell carcinomas HIV-infection in the elderly (>65 years of age) was associated with a higher risk for many cancers identified as HIV-associated in younger populations Most frequently identified cancers were those related to aging Adjusted Hazard Ratios for Cancer Incidence in the Elderly (HIV Infected Versus Uninfected) HR (95% CI) Kaposi sarcoma 79.2 ( ) Non-Hodgkin lymphoma 3.01 ( ) Hodgkin lymphoma 9.96 ( ) Anus 32.4 ( ) Liver 3.83 ( ) Lung 1.52 ( ) Colorectal 0.97 ( ) Breast 0.96 ( ) Prostate 0.78 ( ) Adjusted for race, sex, age, and calender year. Yanik EL, et al. 22 nd CROI. Seattle, Abstract

56 NCI: HIV and Cancer-Specific Mortality in the US ( ) Retrospective analysis of data from 5 US cancer registries (HIV/AIDS Cancer Match study) Cancer-specific mortality by HIV status HIV-infected cancer patients Experienced higher cancer-specific mortality than HIV-uninfected cancer patients for 8 out of 14 cancers Additional 3 cancers (anal, liver, and cervical) had suggested elevations of cancer-specific mortality Adjusted Hazard Ratios for Cancer-Specific Mortality (HIV Infected versus Uninfected) HR (95% CI) Oral cavity/pharynx 1.50 ( ) Colon and rectum 1.69 ( ) Pancreas 1.63 ( ) Larynx 1.92 ( ) Lung 1.28 ( ) Melanoma 1.76 ( ) Breast 2.71 ( ) Prostate 1.83 ( ) Adjusted for age, sex, year of diagnosis, and cancer stage at presentation. Coghill AE, et al. J Clin Oncol. 2015;33:

57 Patients (%) MD Anderson Cancer Center: Efficacy and Safety of ART in Cancer INSTIs were most commonly used in patients concomitantly receiving High-dose steroids, topoisomerase inhibitors, alkylating agents, or antimetabolites 100 ART Efficacy at 6 Months Overall ART-naïve ART experienced 100% 96% 97% 100% 92% 92% INSTI or NNRTI-based ART resulted in increased efficacy and safety without causing significant adverse effects INSTI appear to be preferred when interactions with chemotherapeutic and antifungal agents are anticipated % 67% 60% 78% 78% 20 All patients received NRTIs. 0 INSTI (n=24/12/12) NNRTI (n=31/18/13) PI (n=46/15/30) Other (n=78/78) Torres HA, et al. Clin Microbiol Infect. 2014;20:O672-O679 57

58 D:A:D Study: Risk Factors Associated With Non-AIDS Cancer Mortality in HIV Patients HIV-infected patients (n=33,347) Total deaths (n=2482) Cardiovascular-related: 11.6% Follow-up 180,176 person-years Significant risk factors for non-aids cancers mortality Low BMI, smoking, and age Lower CD4 counts were associated with a higher risk of death Low BMI (<18 kg/m 2 ) Adjusted Rate Ratios for Non-AIDS Cancer Death (95% CI) 2.03 ( ) Smoking 2.20 ( ) Age 1.47 ( ) Need to address modifiable risk factors to further reduce non-aids cancer mortality Smith C, et al. AIDS. 2010;24:

59 Mean %Change/Year in BMD ACTG A5318: Long-Term BMD Changes in ART-Treated Patients Spine and hip BMD Continues to decline with time, but at a significantly slower rate after the first 2 years of ART Predictors of rate of decline in BMD During the first 2 years of ART Mean %Change/Year in BMD P= P=0.99 Related to HIV factors (lower baseline CD4, higher baseline HIV RNA, and FTC/TDF use) During long-term follow-up Lean body mass: 0.05 (spine) and 0.06 (hip) %change/year (P<0.001) -1.5 P< P<0.001 Starting ART at higher CD4 counts may be protective for preservation of bone health Modification of additional risk factors through weight-bearing exercise may prevent further loss -2 Year 0 to 2 Year 2-7 Spine Hip Grant P, et al. J Int AIDS Soc. 2015;18(suppl 4):103. Abstract TUPDB

60 Rate (per 1000 person-years) VA Clinical Case Registry: Osteoporotic Fractures and HAART Retrospective, cohort study ( ; n=56,660) Osteoporotic fracture rate via ICD-9 codes (events/1000 patient-years) Pre-HAART (n=24,221): 1.61 HAART era (n=32,439): 4.09 Factors predicting osteoporotic fracture (HR, multivariate analysis*) Overall cohort White race: 1.88 (P<0.0001) Age: 1.50 (P<0.0001) HCV coinfection: 1.49 (P<0.0001) BMI <20 kg/m 2 : 1.48 (P=0.007) Tobacco use: 1.31 (P=0.003) Specific ART use during HAART era* Tenofovir DF: 1.12 (P=0.011) Lopinavir/r: 1.05 (P=0.051) VA Cohort: Osteoporotic Fracture Rate *Controlled for chronic kidney disease, age, tobacco use, diabetes, and BMI (overall cohort), plus concomitant exposure to other antiretrovirals (specific ART use). Bedimo R, et al. AIDS. 2012;26: Total Hip Wrist Vertebral General population >70 Age at Cohort Entry (years) 60

61 Other Comorbidities in Older HIV-Infected Patients Increased pain Loss of muscle mass Decreasing glomerular filtration rate Hepatic dysfunction Neurocognitive dysfunction Immunosenescence Gebo KA. Drugs Aging. 2006;23: Bhavan KP, et al. Curr HIV/AIDS Rep. 2008;5:

62 Functional Issues With Aging and HIV Frailty phenotype (presence of >3 of the following) Exhaustion, slowed walking speed, low activity level, weakness, and weight loss Associated with poorer health outcomes MACS A 55-year-old HIV-infected person has similar frailty as a 65-year-old HIVnegative person Proposed mechanisms Mitochondrial dysfunction and increased number of free radicals and cytokines activate inflammatory pathways, ultimately leading to frailty Gebo KA, et al. Curr Infect Dis Rep. 2009;11: Desquilbet L, et al. J Gerontol A Biol Sci Med Sci. 2007;62: Oursler KK, et al. AIDS Res Hum Retroviruses. 2006;22:

63 Prevalence (%) MACS: Frailty Phenotype in HIV-Positive MSMs 50 to 70 Years of Age Prospective cohort of MSMs ( ) 10,571 person-visits HIV positive on ART (n=1946) HIV negative (n=1048) Ages 50 to 64 years Frailty phenotype more common in HIV-positive men versus HIVnegative men May be effect of HIV infection, ART, or both Further longitudinal studies are needed Prevalence of Frailty Phenotype 7% HIV-positive on ART HIV-negative 4% 7% 5% 8% 9% 14% 6% 14% 7% < >65 Age Group (years) 18% 10% 24% 17% Althoff KN, et al. J Gerontol A Biol Sci Med Sci. 2014;69:

64 Incidence (%) Risk Factors for Frailty in Aging HIV-Positive Patients Risk Factors (Odds Ratio: Frail Versus Non-Frail) 80 HR: 3.9 P=0.002 Frail (n=33) Pre-frail (n=185) Non-Frail (n=141) HR: 3.9 P<0.001 HR: 3.7 P=0.004 HR: 3.6 P=0.001 HR: 3.3 P= HR: 5.1 P=0.007 HR: 3.8 P=0.067 HR: 3.5 P= Diabetes Neurologic Disease Psychiatric Disease CVD Unhealthy Weight Arthritis Osteoporosis Viral Hepatitis Erlandson KM, et al. 6 th IAS Conference. Rome, Abstract TuPE

65 MINORITY MENTORSHIP PROGRAMS Case Western Reserve University Center for AIDS Research Minority HIV Research Training Program Puerto Rico Comprehensive Center for the Study of HIV Disparities and the Mentoring Institute for HIV and Mental Health Cyber Mentors, funded by National Institute of Mental Health Collaborative HIV Prevention Research in Minority Communities project Center for AIDS Prevention (CAPS) ACTG : Minority HIV Investigator Mentoring Program NIAID SMYAL NIMH Research Education Mentoring Program for HIV/AIDS Researchers HPTN Scholars Program 65

66 Summary: Key Considerations When Caring for Older HIV-Infected Patients ART is recommended in patients >50 years of age, regardless of CD4 count Increased risk of non-aids related complications Immunologic response to ART may be reduced ART-associated adverse events may occur more frequently Closely monitor bone, kidney, metabolic, cardiovascular, and liver health Increased risk of drug-drug interactions between ART and other commonly used medications Regularly assess, especially when starting or switching ART and concomitant medications Coordinate care between HIV experts and primary care providers for older HIVinfected patients with complex comorbidities Counseling to prevent secondary transmission of HIV remains an important aspect of the care of the older HIV-infected patient DHHS. Revision April 8,