PRIMARY CARE ASPECTS PRIMARY CARE ASPECTS OF HIVAnita Fleenor, M.D.

THANK YOUTHANK YOU

Carl B LeBuhn MDCarl B. LeBuhn, MDAndrew R. Hoellein, MD

Who Should be Screened for HIV?

A) Injection Drug UsersA) Injection Drug UsersB) Persons with multiple sexual partnersC) Anyone diagnosed with tuberculosisC) Anyone diagnosed with tuberculosisD) All persons aged 13-64 y/oE) A B d CE) A,B and CF) All of the above

Primary Care Aspects of HIVy p

CDC recommendations for testing

Revised September 2006

Revised Recommendations for HIV Testing of Adults, Adolescents, and Pregnant Women in Health-Care Settings

September 22, 2006 / 55(RR14);1-17

For patients in all health-care settings •HIV screening is recommended for patients in all health-care settings after the patientis notified that testing will be performed unless the patient declines (opt-out screening). •Persons at high risk for HIV infection should be screened for HIV at least annually.

•Separate written consent for HIV testing should not be required; general consentfor medical care should be considered sufficient to encompass consent for HIV testing.

P ti li h ld t b i d ith HIV di ti t ti t•Prevention counseling should not be required with HIV diagnostic testing or as partof HIV screening programs in health-care settings.

R d ti f Ad lt d Ad l t

Screening for HIV Infection

Recommendations for Adults and Adolescents

g

In all health-care settings, screening for HIV infection should be performed routinely for all patients aged 13--64 years.

All patients initiating treatment for TB should be screened routinely for HIV infection (108).

All patients seeking treatment for STDs, including all patients attending STD clinics, should be screened routinely for HIV during each visit for a new complaint, regardless of whether the patient is known or suspected to have specific behavior risks for HIV infectioninfection.

Awareness of Serostatus Among PLWH and Estimates of Transmissionand Estimates of Transmission

~25%~25% Unaware

of Infection

Accounting for: ~54% of New

Infections

~75% AIDS 2006;20:1447 50Aware of Infection

AIDS 2006;20:1447-50

~46% of New

Infections

People Living with HIV/AIDS: ~1,000,000

New Sexual Infections Each Year: ~32,000

Primary Care Aspects of HIVy p

Educate yourself, your staff and the patientEducate yourself, your staff and the patient

HIV is transmitted via sexual contact blood and HIV is transmitted via sexual contact, blood, and sharing needles

HIV is a treatable, chronic disease

Know when to call for help

Primary Care Aspects of HIVy p

StigmaStigmafear and ignorancebehavior that led to HIVbehavior that led to HIV

Cultural Backgroundi i iminorities

Confidentialityrisk of job loss, insurance loss

Rapidly changing field – easier to refer/transfer

Conspiracy Beliefs about HIV/AIDSHIV/AIDS

f 00 fTelephone survey of 400 African-Americans

Bogart LM and Thorburn S. JAIDS. 2005;38(2):213-218.

What is the estimated life expectancy of a male diagnosed with HIV in 2009?diagnosed with HIV in 2009?

A) 10 yearsA) 10 yearsB) 17 yearsC) 22 yearsC) 22 yearsD) 30 years

Life Expectancy for persons with HIV

PLWHPLWH

Causes of Death among Persons with AIDS inCauses of Death among Persons with AIDS in the Era of Highly Active Antiretroviral Therapy– All adult NYC residents with AIDS 1999-2004All adult NYC residents with AIDS 1999 2004– Cohort analysis, death certificates– Non-HIV deaths ↑32.8% (19.8-26.3, p=.0015)↑ ( , p )

• Substance abuse – 31%• CVD – 23.8%• Cancer 20 8%• Cancer – 20.8%

– Age-adjusted mortality for AIDS ↓49.6/10,000/year (p<.0001)

Sackoff JE, Hanna DB, Pfeiffer MR, Torian LV. Ann Intern Med. 2006;145:397-406

Consider Testing for HIVg

Fatigue Thrombocytopenia

Patient Complaints Patient Labwork

Weight loss Leukopeniag

Night Sweats

p

AnemiaNight Sweats

Diarrhea

Anemia

Elevated ProteinDiarrhea Elevated Protein

M ll

Umbilicated center

Molluscum contagiosum

M llMolluscum contagiosum

S b h DSeborrheic Dermatitis

S b h dSeborrheic dermatitis

A HIV

Violaceous macular and papular

Acute HIV

O l d dOral candidiasis

S Severe psoriasis

Primary Care Aspects of HIVy p

RPRRPRTestosteroneBone Density?Bone Density?CBC- increased leukopenia, anemia and thrombocytopeniathrombocytopeniaGlucose – increased prevalenceUA d l l d C Cl ( di CG)UA and calculated CrCl (most studies use CG)TB screen (5 mm or close contact with active case)

Primary Care Aspects of HIVy p

Lipids ( HIV meds and HIV itself assoc. with)Lipids ( HIV meds and HIV itself assoc. with)Hepatitis Serology – and vaccinate if indicatedPap q 6 months X 2 then annual (anal pap?)Pap – q 6 months X 2 then annual (anal pap?)Renal (kidney function abnl in up to 30%)C diCardiacOsteoporosisCancersDrug drug interactions

Trends in standard incident rates in 3 AIDS-defining and 9 AIDS non9 AIDS non-defining types of cancer among

fHIV-infected persons and the general population g p pstratified by 3 periods from 1992-20032003.

Patel et al. Ann Intern Med. 2008;148:728-736

CounselingCounseling

• Safer sex practices• Substance Use• Tobacco use• Reproductive Health• Reproductive Health• Psychosocial Assessment

I C t t L l I– Insurance, Contacts, Legal Issues• Diet and ExerciseHIV Guidelines: New York State Department of Health AIDS Institute, 2009. http://www.hivguidelines.org/Content.aspx

CASECASE Year Total HDL LDL TriglyceridesYear Cholesterol HDL LDL Triglycerides

2003 179 31 412

2004 265 30 743

2005 161 29 101 156

2006 153 23 84 231

2007 166 29 73 3192007 166 29 73 319

2008 208 36 89 700

2009 227 46 107 3702009 227 46 107 370

PLWH and Dyslipidemia

• Untreated HIV: ↑TG and ↓HDL

• HAART: ↑TC and ↑TG ( > )• HAART: ↑TC and ↑TG ( > )– HDL may increase with NNRTIs

Oth PI t i did t h– Other PI atazanavir did not change endothelial dysfunction despite improved lipid profilelipid profile

• FLP before and 3-6 months after HAARTAHRQ National Guideline Clearinghouse. Infectious Disease Society of America. Mod 5/23/2005.

Flammer AJ, Vo NT, et al. Heart. 2009;95(5):385-90.

PLWH and D li id iDyslipidemia

Other recommendations:• Δ PI to nevirapine or abacavir (C-III)• ‘Statin for LDL and TG 200-500 (B-I)• Fibrates less optimal (C-I TC/LDL, B-I TG)• Avoid niacin and bile-sequestering resins (C-III)

– Niacin increases risk of glucose intolerance• Fish oils may be tried (C-III)

– Can combine with fibrates if necessary

Aberg JA. Lipid Management in Patients who have HIV and are Receiving HIV Therapy. Endocrinol Metab Clin N Am. 2009;38:207-222.

PLWH and DyslipidemiaPLWH and Dyslipidemia

Atorvastatin (Lipitor®)Ezetimibe (Zetia®)

Simvastatin (Zocor®) Lovastatin (Mevacor®)

Niacin (Niaspan®)Ω-3 Fatty Acids (Omacor®)

Cholestyramine(Questran®)

Colestipol (Colestid®)

Pravastatin (Pravachol®)Rosuvastatin (Crestor®)Rosuvastatin (Crestor®)Gemfibrozil (Lopid®)Fenofibrate (Lofibra®)

PLWH and Heart DiDisease

• HIV infection 1.5-2 x risk CAD– Younger (x=50)– Lower TIMI risk scores– Single vessel disease– Higher rate stent complications

• Initiation of HAART in treatment-naïveInitiation of HAART in treatment naïve short-term risk reduction

• Long-term PI use increased risk• Long-term PI use increased risk

Ho JE, Hsue PY. Cardiovascular Manifestations of HIV Infection. Heart. 2009;95:1193-1202.

Primary Care for Patients with HIV/AIDSCardiovascular Disease

All PLWH h ld b l d f CAD i kAll PLWH should be evaluated for CAD riskTraditional risk factors

tobacco HTN dyslipidemia family historytobacco, HTN, dyslipidemia, family historyEmerging risk factors

weight, HAART (PIs)

TreatmentLifestyle modification

smoking cessationTreat diabetes, HTN, dyslipidemiaLow CV risk HAARTLow CV-risk HAART

CASE

Presents in 3/07/Low back and hip painHurts anterior and medial thighSome pain in the groinPlain films negativeMRI lumbar spine negativeNo response to NSAIDS

CASE

PLWH and Bone Disorders

• Prevalence– Osteopenia in HAART-naïve = 23-28%– Osteoporosis (OP) with PIs = 50%

(vs. 23% HIV+ off PIs)– No increased rate of fragility fractures– Osteonecrosis (ON) = 4.4% of 339

asymtomatic patients

Morse CG, Kovacs JA. Metabolic and Skeletal Complications of HIV Infection. JAMA. 2006;296:844-854.

PLWH and Bone Disorders

• Pathophysiology– Low BMI, smoking, alcohol, steroids1

– Hypogonadism1

– Duration of HIV (OP)1

– Lipid oxidation products (OP)2

– Viral load (OP)3( )– HIV and HAART not independent RF for ON1

1Morse CG, Kovacs JA. Metabolic and Skeletal Complications of HIV Infection. JAMA. 2006;296:844-854.2Wiercinska-Drapalo, A, et al. Infection. 2007;35:46-48.3Fausto A, et al. Bone. 2006;38:893-897

CASE• 53 year old man

followed since 2001• Hospitalized 1/09 with

severe depression– Lowest CD4 170– Currently well

p• Recently homeless• Family turmoil

controlled on trizivirand kaletra

– 30 pound weight Year Highest Glucose30 pound weight

gain• Past Medical History

Glucose2001 822003 134

– AIDS– Depression

2003 1342005 1382007 147

– HTN– Syphylis

GERD

2009 222

PLWH and DiabetesPLWH and Diabetes

• Insulin resistance and impaired glucose tolerance in up to 50% of PLWH on PIs1

M 4 i k d t ti 2• Men – >4x risk compared to seronegative men2

• Diagnosis– Fasting glucose >126, random >200– Insulin levels and GTT* not currently

d drecommended

1. Grinspoon S, Carr A. Cardiovascular Risk and Body-Fat Abnormalities in HIV-Infected Adults. NEJM. 2005;352;48-62.2. Brown TT, Cole SR, et al. Antiretroviral Therapy and Prevalence and Incidence of Diabetes Mellitus in the Multicenter AIDS Cohort Study. Arch Intern Med. 2005;165:1179-84.

PLWH and Lipodystrophy

Li d t h• Lipodystrophy– Subcutaneous lipoatrophy ( > )

F• Face• Extremities• ButtocksButtocks

– Accumulation of central fat ( > )• Visceral fat• Dorsocervical fat pad, breasts, lipomatosis

• Lipodystrophy Syndrome– with insulin resistance and dyslipidemia

Morse CG, Kovacs JA. Metabolic and Skeletal Complications of HIV Infection. JAMA. 2006;296:844-854.

LipodystrophyLipodystrophy

PLWH and Lipodystrophy

• Prevalence– 20-84%– 20-50% will develop at least 1 sign of

lipodystrophy within 2 years of HAART• Pathophysiology

– Mitochondrial toxicity impaired ATPy p– NRTIs (stavudine > AZT >> ABC/TDF)– PIs (except atazanavir)( p )

Morse CG, Kovacs JA. Metabolic and Skeletal Complications of HIV Infection. JAMA. 2006;296:844-854.

THE END

PLWH and Bone Di dDisorders

Screening - suggested

Paccou J, et al. Bone Loss in Patients with HIV Infection. Joint Bone Spine. 2009;76:637-41.

M ll

Umbilicated center

Molluscum contagiosum

S b h DSeborrheic Dermatitis

CASE CASE

Year Total HDL LDL TriglycerideYear Cholesterol HDL LDL s

2003 179 31 412

2004 265 30 743

2005 161 29 101 156

2006 153 23 84 231

2007 166 29 73 3192007 166 29 73 319

2008 208 36 89 700

2009 227 46 107 3702009 227 46 107 370

Aberg JA. Lipid Management in Patients who have HIV and are Receiving HIV Therapy. Endocrinol Metab Clin N Am. 2009;38:207-222.

Anxiolyticsy

Avoid: triazolam and midazolam Consider: short-acting agents Consider: short acting agents -Lorazepam (Ativan®) Oxazepam (Serax®)-Oxazepam (Serax®)

Consider: Buspirone (Buspar®)Al l (X ®) h ld b Alprazolam (Xanax®) should be used cautiously with ritonavir

PLWH and Dyslipidemia

Lipid-lowering drugs:• HMG-CoA Reductase Inhibitors

– Most metabolized by CYP3A4– Simvastatin and lovastatin should not be used if on

PIs or delavirdinePIs or delavirdine– use atorvastatin with caution

• Drug-drug interactions unlikely with fibratesDrug drug interactions unlikely with fibrates• Ezetimibe

– efficacious, tolerated, interactions unlikelyefficacious, tolerated, interactions unlikely– clinical outcome data?

Negredo E, et al. AIDS. 2006;20:2159-2164; Coll B, et al. AIDS. 2006;20:1675-1677

Bone Disorders

Treatment strategiesMaintain dietary calcium and vitamin DIncorporate weight bearing exerciseBisphosphonate therapy combined with calcium and vitamin DJoint replacement therapy

PLWH and Metabolic Complications

• Higher risk for development of hyperglycemia, dyslipidemia, and cardiovascular diseaseC l th h i l• Complex pathophysiology– PI inhibition of SREBP-mediated PPAR-γ expression

NRTI inhibition of mitochondrial DNA polymerase γ– NRTI inhibition of mitochondrial DNA polymerase γ– Increased lpC-II and lpE, decreased lpD degredation

Impaired FA oxidation ± circulating FA storagep g g• Decreased glucose phosphorylation

– Decreased GLUT-4

Grinspoon S, Carr A. Cardiovascular Risk and Body-Fat Abnormalities in HIV-Infected Adults. NEJM. 2005;352;462)..

Insulin Resistance and DiabetesInsulin Resistance and Diabetes

Insulin resistance and glucose intolerance greported in up to 50% of patients on HAART (PI)HIV (+) men on HAART are 4X more likely to ( ) ydevelop diabetes compared with HIV (-) controlsSymptoms may develop within a few weeks of y p y pstarting treatmentFactor in risk factors for DM in choosing HAART gstrategy

Grinspoon S Carr A Cardiovascular Risk and Body-Fat AbnormalitiesGrinspoon S, Carr A. Cardiovascular Risk and Body-Fat Abnormalities in HIV-Infected Adults. NEJM. 2005;352;48-62AAHIVM Fundamentals of HIV Medicine 2007, 845-6

Bone DisordersHigh prevalence of Osteopenia and OsteoporosisHigh prevalence of Osteopenia and Osteoporosis

One osteoporosis prevalence study in treatment naïve patients:p

23 to 28% higher than HIV(-) controls

Study osteoporosis rates in patients on treatmentStudy osteoporosis rates in patients on treatment:50% in patients receiving PI23% in HIV patients not on PI29% in matched controls

One studyOne studyHigh prevalence (4.4%) osteonecrosis of the hip (asymptomatic patients)Symptomatic osteonecrosis of the hip 100X higher than Symptomatic osteonecrosis of the hip 100X higher than the general population

Metabolic and Skeletal Complications of HIV Infection. JAMA. 2006;296:844-854.AAHIVM Fundamentals of HIV Medicine 2007, 845-6