HIV Infection as a Chronic Disease. Howard Libman, MD Beth Israel Deaconess Medical Center Harvard Medical School

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1 HIV Infection as a Chronic Disease Howard Libman, MD Beth Israel Deaconess Medical Center Harvard Medical School

2 Role of Primary Care Approximately 50,000 patients are diagnosed with HIV infection annually in the United States, and the number of people living with HIV infection continues to increase Recent guidelines advocate earlier initiation of antiretroviral therapy HIV-infected patients are living longer, and some will develop complications of therapy and other comorbid conditions Along with these patients, the first generation of HIV practitioners is maturing, and many will retire over the next 10 years Future primary care practitioners will have substantial responsibility for the care of this patient population

3 Increasing Prevalence of Persons Living with HIV/AIDS Institute of Medicine, HIV Screening and Access to Care, 2011.

4 Increased HIV Screening of Population Increased Survival of HIV-Infected Patients Increased Number of Patients, Many on Antiretroviral Therapy, Requiring HIV Care Aging of Patient Population and Development of Long-Term Treatment Complications and Comorbid Medical Conditions Need for Increased Primary Care Involvement in HIV Care Decreased Capacity for Provision of Primary Care to HIV-infected Patients Decreased Number of Medical Residents Pursuing Primary Care Inadequate Training of Medical Residents in HIV Outpatient Medicine First Generation of HIV Practitioners Nearing Retirement in Next 10 Years

5 One of the challenges is the emergence of HIV as a chronic medical condition, increasing the complexity of treating HIV-positive individuals Infectious disease specialists may, as a rule, have greater expertise than primary care providers in treating HIV, but increasingly HIV-positive patients require the broader skills of primary care physicians, APRNs, and PAs to address their other health care needs. Institute of Medicine, HIV Screening and Access to Care: Health Care System Capacity for Increased HIV Testing and Provision of Care, 2011.

6 Primary Care Characteristics of HIV Infection HIV infection is chronic, multisystem, and has a spectrum of manifestations Standardized intake, stratified management, and common clinical problems Patient care requires the availability of: nursing support social service subspecialty consultation mental health/addiction professionals clinical trials Multidisciplinary approach is optimal for patients and practitioners

7 Primary Care Practitioner Roles in HIV Care Universal HIV screening and prevention Antiretroviral therapy* and medication adherence Prophylaxis of opportunistic infections Management of comorbid conditions Health care maintenance Immunizations Other HIV-related health care maintenance issues Age- and sex-related health care maintenance issues * Involvement may vary depending upon interest and experience of primary care practitioners and availability of HIV specialists

8 What percentage of diagnosed HIV-infected patients in the US has a suppressed viral load? 1. 77% 2. 51% 3. 45% 4. 35%

9 Overview of HIV Care and Treatment in the United States 100% 80% 60% 40% 20% 0% Diagnosed HIV Patients Linked to Care Remained in Care Prescribed Antiretroviral Therapy Viral Load Suppressed MMWR. 2011;60(47):

10 Long-Term Complications Lipodystrophy syndrome Premature atherosclerosis Lactic acidemia/acidosis Premature bone loss Avascular necrosis of the hips Peripheral neuropathy

11 LDS Clinical Manifestations Lipid metabolism Increased triglycerides Increased cholesterol, LDL, cholesterol/hdl ratio Decreased HDL Glucose metabolism Insulin resistance Glucose intolerance Diabetes mellitus Fat accumulation Increased visceral fat Buffalo hump Lipomatosis Gynecomastia Fat atrophy Face, extremities, buttocks

12 Management of Lipodystrophy Syndrome Hyperlipidemia, insulin resistance Visceral fat accumulation Subcutaneous fat wasting Diet and exercise Switch therapy Older PI atazanavir or NNRTI Statins/fibrates Insulin-sensitizing drugs Diet and exercise Switch therapy Older PI NNRTI Growth hormone or growth hormone releasing factor Cosmetic surgery Switch therapy Older PI NNRTI Insulin-sensitizing drugs Local injection (polylactic acid, calcium hydroxylapatite)

13 HIV Infection and Coronary Artery Disease Incidence of CAD is relatively low but higher than that in HIV-negative patients matched for age and gender Degree to which HIV infection itself, antiretroviral therapy, and traditional risk factors contribute to increased risk in this population is unknown PI class appears to be associated with higher risk of CAD; data regarding abacavir are inconsistent Discontinuation of ART is associated with higher risk of CAD High prevalence of traditional risk factors in this population

14 Major Risk Factors for Coronary Artery Disease Age (men 45 years, women 55 years) High LDL cholesterol (> 160 mg/dl)* Low HDL cholesterol (< 40 mg/dl) Hypertension Family history of premature coronary artery disease (CAD) Diabetes mellitus (DM) Cigarette smoking * With CAD, DM, or multiple risk factors, the desirable level for LDL cholesterol decreases; <100 mg/dl is ideal. Grundy SM et al. JAMA. 2001;285:

15 HIV infection is associated with the following increased percentage risk of acute myocardial infarction beyond that explained by recognized risk factors: 1. 90% 2. 70% 3. 50% 4. 30%

16 The Risk of Coronary Artery Disease in HIV-infected Patients Freiberg MS et al. JAMA Intern Med. 2013;173:

21 Premature Bone Loss (1) Osteopenia, osteoporosis, and pathological fractures have been described Osteopenia is asymptomatic, whereas osteoporosis may present with fractures of vertebrae, forearms, or hips Tenofovir, alterations in vitamin D metabolism, and lactic acidemia from NRTI therapy may be responsible for bone loss HIV infection itself may also be a contributing factor

22 Premature Bone Loss (2) Immobility, cigarette smoking, excessive alcohol use, chronic renal disease, hypogonadism, hyperparathyroidism, hyperthyroidism, and steroid use accentuate bone loss Utility of bone densitometry in patients on antiretroviral therapy without other risk factors for premature bone loss is uncertain Calcium and vitamin D should be given in high-risk patients; regular exercise and smoking cessation should be advised

23 Antiretroviral Exposure and Risk of Osteoporotic Fractures Bedino R et al. AIDS. 2012;26:

24 Exposure to Specific Protease Inhibitors and Risk of Osteoporotic Fractures Bedino R et al. AIDS. 2012;26:

25 Screening for Long-Term Complications Glucose Intolerance/Diabetes Mellitus Fasting glucose and/or HgbA1c every 6-12 months Lipid Abnormalities Fasting lipid profile every 6-12 months Body Fat Maldistribution Patient self-report, weight at each visit, and anthropometric measurements (skin fold, waist, and hip) periodically Lactic Acidemia/Acidosis Venous lactic acid level only in symptomatic patients Premature Bone Loss Baseline bone densitometry in post-menopausal women and in men at age 50 Avascular Necrosis of Hips X-rays and MRI only in symptomatic patients

26 Which of the following statements is false about HIV-infected patients over 50 years of age? 1. They present with an earlier stage of disease 2. They constitute 30 percent of HIV-infected patients 3. They are at increased risk of cognitive impairment compared to general population 4. They are at increased risk of common malignancies compared to general population

27 HIV HIV Infection Infection in in the the Older Older Patient Patient (1) (1) Approximately 30% of HIV-infected persons are 50 years of age Limited data on effects of ART in older persons Older persons may be diagnosed later and have more advanced HIV at presentation Medication adherence is generally good

28 Chronic Complications by Age and HIV Status Guaraldi G et al. Clin Infect Dis. 2011;53:

29 HIV Infection in the Older Patient (2) HIV-infected patients accumulate age-related diseases at younger age Neurocognitive disorders and non AIDS-defining cancers are also more prevalent Hypothesis that increased immune activation and long-term chronic inflammation contribute to premature aging in this population Independent risk factors include age, male sex, nadir CD4+ cell count below 200/µL, and antiretroviral therapy

30 Causes of Death in the Modern Era Retrospective study of 39,272 patients in 13 cohorts between In 1597 (85%) of 1876 deaths, cause was identified 49.5% of deaths were AIDS-related, 11.8% were from non-aids malignancies, 8.2% were from non-aids infections, 7.7% were violence- and/or drug-related, 7.0% were from liver disease, and 6.5% were from cardiovascular disease Death rate was higher in patients with history of injection drug use with liver and respiratory diseases responsible for many cases Antiretroviral Therapy Cohort Collaboration. Clin Infect Dis. 2010;50:

31 Figure 1 Antiretroviral Therapy Cohort Collaboration. Clin Infect Dis. 2010;50:

32 Figure 2 Antiretroviral Therapy Cohort Collaboration. Clin Infect Dis. 2010;50:

33 Figure 3 Antiretroviral Therapy Cohort Collaboration. Clin Infect Dis. 2010;50:

34 Summary Primary care practitioners have a significant role in the care of HIVinfected patients Long-term complications associated with HIV infection and its treatment, including coronary artery disease and premature bone loss, will become increasingly common over time HIV-infected patients should be assessed for cardiovascular risk, and modifiable factors should be identified and addressed Baseline bone densitometry should be performed in post-menopausal HIV-infected women and in HIV-infected men > 50 years old Understanding the effect of HIV infection on aging is important in managing older patients with this disease As HIV-infected patients live longer, traditional age-related diseases will account for an increasing percentage of deaths

Primary Care of the HIV-infected Adult: If I Can Do It, You Can Do It

Primary Care of the HIV-infected Adult: If I Can Do It, You Can Do It Howard Libman, MD Professor of Medicine, Emeritus Harvard Medical School Boston, Massachusetts Learning Objectives After attending