INITIATING OR RESTARTING THERAPY-PART TWO

1. I. Jean Davis, PhD, PA, AAHIVS Howard University College of Medicine INITIATING OR RESTARTING THERAPY-PART TWO

2. Objectives • Discuss the need and clinical process of initiating or restarting ART. • Discuss the benefits of antiretroviral therapy in reducing mortality and/or AIDS-related morbidity. • Discuss the role of ART in reducing the risk of disease progression in individuals infected with HIV. • Discuss the role of  ART in the prevention of transmission of HIV for individuals infected with HIV.

3. Clinical Case Study #1 • Mr. Martin is a 35 year old Black Hispanic male, diagnosed with HIV 10 years ago. He has never taken ART. He self-identifies as heterosexual but admits to having sex with men. He has been incarcerated approximately 6 of the past 10 years, and released 18 months ago. He is married and has a 12 year old son, a 9 year old daughter and twin boys 6 months old. His wife works for the local cable company. He is presently working with his mother’s brother painting houses. He admits to poly-drug use with methamphetamine IV as his drug of choice. He denies any additional medication history other than an abdominal GSW 11 years ago and multiple stab wounds to the chest 5 years ago during a fight while incarcerated. He states that he does not use condoms during any sexual activities with his wife or male associates, explaining he has only had given anal sex .

4. Clinical Case Study #1 • Mr. Martin states he has a family history of cardiovascular disease and diabetes. He is the 4th child of 7 children. His father was an alcoholic and died from liver disease at age 45. His mother was diagnosed with diabetes and heart disease during her early 40s. Her right leg was amputated at age 58 due to complications. She is presently on medication for heart disease and diabetes. She was recently placed on dialysis. Four of his siblings were killed associated with gang violence. His older sister is a nurse and younger brother is in the military.

5. Half of Deaths in HIV-Infected Patients Now Due to Non-AIDS-Related Causes Cause of Death in HIV+ Individuals Initiating ART (Europe and North America, 1996-2006, n=1597*) *N=39,272; total deaths=1876. Antiretroviral Therapy Cohort Collaboration Clin Infect Dis. 2010;50:1387-1396.

6. Hepatitis

7. Hepatitis: Definition • Inflammation of the liver caused by many different agents, including: • Viruses (A through E) • Alcohol • Drugs: Illegal and/or Prescription • Herbs • Genetic disorders • Obesity (NASH)

8. Major Hepatitis Viruses

9. Prevalence of HCV Infection:Selected Subgroups in the U.S. • Injection drug users: 52-90% • Hemophiliacs: 60-85% • HIV infected individuals: 9-40% • Incarcerated HIV+: 50% • MSM: 4-8%

11. Cancer

12. The Burden of Cancer Among HIV-infected Persons in The US Population Non-AIDS-defining Cancers in People with AIDS in the U.S. 700 2500 2250 600 Incidence Rate per 100,000 2000 2191 Number of Cases 1750 500 1500 400 1250 7869 300 1000 5327 750 200 500 100 250 0 0 1991 1992 1993 1995 1997 1998 1999 2000 1994 2001 2003 2005 1996 2002 2004 453 Data for 34 U.S. States (2004-2007) Shiels M, et al. 18th IAC; Vienna, July 18-23, 2010; Abst. WEAB0101

13. Diabetes

14. Metabolic Syndrome HIV+ Patients • Up to 40% of patients treated for HIV-1 infection have abnormal glucose metabolism with evidence of insulin resistance. • Obesity and hypertension are frequently seen in black patients as part of the metabolic syndrome. • Metabolic syndrome is a constellation of abnormalities that include high waist circumference, elevated triglycerides, low HDL-C, hypertension, and glucose intolerance.

15. Diabetes Mellitus HIV-Infected Patients Identifying the Problem • Cumulative exposure to NRTIs, not NNRTIs or PIs, correlated with fasting insulin resistance markers: • Strongest association with Epivir (lamivudine) and Zerit (stavudine). • Increasing BMI significantly associated with more insulin resistance.

16. Diabetes Mellitus HIV + Patients • HIV disease and treatment may add to the risk. • Long-term changes in glucose metabolism: • Direct effects in vitro and in vivo1-4 • Role of HIV or disease stage not known •  fasting glucose concentrations over time associated with PI class

17. Neuropathy

18. Peripheral Neuropathy • Peripheral neuropathy is the most prevalent neuropathy associated with HIV/AIDS, and is now the commonest neurological complication of HIV infection. • Studies performed prior to the availability of antiretroviral therapy documented affecting over one-third of AIDS patients, with the introduction of NRTI potentially neuro-toxic antiretroviral agents. • Although increasing prevalence in the face of declining rates of almost all other neurological complications of HIV since the introduction of combination antiretroviral.

19. Heart Disease

20. HIV Related Morbidity and Mortality • From a public health stand point, MI and other CVD events are a relatively smaller issue in HIV positive patients when compared to overall HIV related morbidity & mortality. • Most guidelines support maximal viral suppression and increased immune function: • Increasing CD4+ cell count to levels approaching un-infected controls may reduce all-cause mortality, as well as HIV-related mortality.

21. Management of HIV Patients At Risk for Heart Disease • Current guidelines support treating Heat Disease risk in HIV+ patients in the same manner as recommended for the general population: • Smoking • Recreational Drugs: Vasoconstriction or Increase HR • Risk for heart disease in persons with two or more risk factors: • Elevated lipids • Elevated blood pressure

22. Kidney Disease

23. HIV Related Kidney • Although HIVAN is the classic kidney disease of HIV infection, several other forms of kidney disease have also been associated with HIV. • Particularly in the early years of the epidemic, patients with AIDS were observed to be at increased risk for clots in small blood vessels (systemic thrombotic microangiopathy: TMA). • HIV infection has also been suggested for nephropathy and other forms of immune complex: • Co-infections such as the hepatitis viruses and syphilis have also been associated with glomerular disease, and • Hepatitis C virus co-infection in particular has been linked to an increased risk for kidney disease

24. HIV Related Kidney • The treatment of HIV and associated infections may also be complicated by kidney disease. • Although several antiretroviral agents have been implicated in isolated cases of acute or chronic kidney injury, only the protease inhibitor indinavir (Crixivan) and the nucleotide reverse transcriptase inhibitor tenofovir (Viread) have been linked to a consistent pattern of nephrotoxicity. • Both HIV infection and ART have also been associated with an increased risk for traditional renal risk factors such as diabetes and hypertension.

25. HIV Related Kidney • With improved survival and aging of the HIV-infected patient population co-morbid diabetic and hypertensive nephropathy are likely to overtake HIVAN as the leading causes of Chronic Kidney Disease (CKD) and End Stage Renal Disease (ESRD). • With improved survival and aging of the HIV-infected patient population co-morbid diabetic and hypertensive nephropathy are likely to overtake HIVAN as the leading causes of Chronic Kidney Disease (CKD) and End Stage Renal Disease (ESRD).

26. Questions?

27. Clinical Case Study #1 • Mr. Martin is a 35 year old Black Hispanic male, diagnosed with HIV 10 years ago. He has never taken ART. He self-identifies as heterosexual but admits to having sex with men. He has been incarcerated approximately 6 of the past 10 years, and released 18 months ago. He is married and has a 12 year old son, a 9 year old daughter and twin boys 6 months old. His wife works for the local cable company. He is presently working with his mother’s brother painting houses. He admits to poly-drug use with methamphetamine IV as his drug of choice. He denies any additional medication history other than an abdominal GSW 11 years ago and multiple stab wounds to the chest 5 years ago during a fight while incarcerated. He states that he does not use condoms during any sexual activities with his wife or male associates, explaining he has only had given anal sex .

28. Clinical Case Study #1 • Mr. Martin states he has a family history of cardiovascular disease and diabetes. He is the 4th child of 7 children. His father was an alcoholic and died from liver disease at age 45. His mother was diagnosed with diabetes and heart disease during her early 40s. Her right leg was amputated at age 58 due to complications. She is presently on medication for heart disease and diabetes. She was recently placed on dialysis. Four of his siblings were killed associated with gang violence. His older sister is a nurse and younger brother is in the military.

29. Clinical Case Study #1 • What PE findings may be significant? • What lab findings may be significant? • What co-morbidities may be found based on history, PE and lab findings?

30. Clinical Case Study #1 • Significant PE and Lab Results: • Ht:5:0 Wt: 186 lbs B/P: 160/92 • CD4: 194 • VL: 50,000 • Genotype: Negative • HVC: Positive • Syphilis: 1:8 • Glucose: 258 • GFR: 50 • LDL: 300 • HDL: 26 • PSA: 3.8

31. Clinical Case Study #1 • What additional history do we need? • What additional lab tests should we order? • What co-morbidities are our concerns? • What impact would ART have on his quality of life and health? • What health promotion, disease prevention education would you provide for Mr. Martin? • Wife • Children • Lifestyle

32. Resources • www.aetcnmc.org • www.capitolregiontelehealth.org

33. Howard University HURB 1 1840 7th Street NW, 2nd Floor Washington, DC 20001 202-865-8146 (Office) 202-667-1382 (Fax) www.capitolregiontelehealth.org www.aetcnmc.org