I. Jean Davis, PhD, PA, AAHIVS Howard University College of Medicine

 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.

 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.

 Mr. Martin states he has a family history of cardiovascular disease and diabetes. He is the 4 th 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.

*N=39,272; total deaths=1876. Cause of Death in HIV+ Individuals Initiating ART (Europe and North America, , n=1597*) Antiretroviral Therapy Cohort Collaboration Clin Infect Dis. 2010;50:

 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)

VirusMeans of transmission Hepatitis AFecal-oral: Contaminated food or water Hepatitis BSexual, mother-to-child, blood exposure (transfusion, IDU, tattoo) Hepatitis CBlood exposure (transfusion, IDU, tattoo); sexual, mother-to-child less common

 Injection drug users: 52-90%  Hemophiliacs: 60-85%  HIV infected individuals: 9-40%  Incarcerated HIV+: 50%  MSM: 4-8%

Data for 34 U.S. States ( ) Non-AIDS-defining Cancers in People with AIDS in the U.S. ■ 0-12 yrs ■ yrs ■ yrs ■ yrs ■ yrs ■ yrs ■ 60+ yrs Shiels M, et al. 18 th IAC; Vienna, July 18-23, 2010; Abst. WEAB0101

 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.

 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.

 HIV disease and treatment may add to the risk.  Long-term changes in glucose metabolism:  Direct effects in vitro and in vivo 1-4  Role of HIV or disease stage not known   fasting glucose concentrations over time associated with PI class

 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.

 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.

 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

 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

 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.

 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).

 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.

 Mr. Martin states he has a family history of cardiovascular disease and diabetes. He is the 4 th 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.

 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?

 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

 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

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